Issue 44, December 14, 2020

CDC Science Clips: Volume 12, Issue 44, December 14, 2020

Science Clips is produced weekly to enhance awareness of emerging scientific knowledge for the public health community. Each article features an Altmetric Attention scoreexternal icon to track social and mainstream media mentions.

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Comparison of several survey-based algorithms to ascertain type 1 diabetes among US adults with self-reported diabetesexternal icon
        Casagrande SS, Lessem SE, Orchard TJ, Bullard KM, Geiss LS, Saydah SH, Menke A, Imperatore G, Rust KF, Cowie CC.
        BMJ Open Diabetes Res Care. 2020 Dec;8(2).
        INTRODUCTION: Defining type of diabetes using survey data is challenging, although important, for determining national estimates of diabetes. The purpose of this study was to compare the percentage and characteristics of US adults classified as having type 1 diabetes as defined by several algorithms. RESEARCH DESIGN AND METHODS: This study included 6331 respondents aged ≥18 years who reported a physician diagnosis of diabetes in the 2016-2017 National Health Interview Survey. Seven algorithms classified type 1 diabetes using various combinations of self-reported diabetes type, age of diagnosis, current and continuous insulin use, and use of oral hypoglycemics. RESULTS: The percentage of type 1 diabetes among those with diabetes ranged from 3.4% for those defined by age of diagnosis <30 years and continuous insulin use (algorithm 2) to 10.2% for those defined only by continuous insulin use (algorithm 1) and 10.4% for those defined as self-report of type 1 (supplementary algorithm 6). Among those defined by age of diagnosis <30 years and continuous insulin use (algorithm 2), by self-reported type 1 diabetes and continuous insulin use (algorithm 4), and by self-reported type 1 diabetes and current insulin use (algorithm 5), mean body mass index (BMI) (28.6, 27.4, and 28.5 kg/m(2), respectively) and percentage using oral hypoglycemics (16.1%, 11.1%, and 19.0%, respectively) were lower than for all other algorithms assessed. Among those defined by continuous insulin use alone (algorithm 1), the estimates for mean age and age of diagnosis (54.3 and 30.9 years, respectively) and BMI (30.9 kg/m(2)) were higher than for other algorithms. CONCLUSIONS: Estimates of type 1 diabetes using commonly used algorithms in survey data result in varying degrees of prevalence, characteristic distributions, and potential misclassification.

      2. Survey of teen noise exposure and efforts to protect hearing at school - United States, 2020external icon
        Eichwald J, Scinicariello F.
        MMWR Morb Mortal Wkly Rep. 2020 Dec 4;69(48):1822-1826.
        Noise-induced hearing loss (NIHL) is a substantial, often unrecognized, health problem. Various learning environments and activities in school settings are loud. Researchers have reported the prevalence of NIHL among U.S. adolescents ranging between 12.8% and 17.5%, suggesting that one in every six to eight middle and high school students (aged 12-19 years) has measurable hearing loss likely resulting from excessive noise exposure (1). Evidence suggests that even mild levels of hearing loss negatively affect auditory perception and cognitive skills.* CDC analyzed data from a sample of 817 youths aged 12-17 years who responded to the web-based YouthStyles survey in 2020. The survey measured the frequency of exposure to loud noise in school settings, the provision of hearing protection devices (HPDs) during exposure, and whether prevention techniques were part of their educational curriculum. Approximately three in four teenage students reported being exposed to loud sound at school, and nearly one half (46.5%) of respondents reported exposure to loud sounds at school on a regular basis. A majority of students (85.9%) reported that their school did not provide HPDs during classes or activities where they were exposed to loud sounds, and seven out of 10 reported they were never taught how to protect their hearing. Increasing youth's awareness about the adverse health effects of excessive noise exposure and simple preventive measures to reduce risk can help prevent or reduce NIHL. Health care providers and educators have resources and tools available to prevent NIHL among school-aged children. Increased efforts are needed to promote prevention.

      3. Plasma cell myeloma (also called multiple myeloma), solitary plasmacytoma, and extramedullary plasmacytoma are primarily diseases of the elderly. Evidence suggests an association between excess body weight and multiple myeloma. Few population-based studies have examined incidence and mortality of each site in one study. We analyzed incidence and death rates by site (solitary plasmacytoma, extramedullary plasmacytoma, and multiple myeloma) by gender, age, race/ethnicity, and rural-urban status among adult males and females (aged 20 years or older) in the United States during 2003-2016. Trends were characterized as average annual percentage change (AAPC) in rates. During 2003-2016, overall incidence rates among adults were 0.45 for solitary plasmacytoma, 0.09 for extramedullary plasmacytoma, and 8.47 for multiple myeloma per 100,000 persons. Incidence rates for multiple myeloma increased during 2003-2016 among non-Hispanic whites (AAPC = 1.78%) and non-Hispanic blacks (2.98%) 20-49 years of age; non-Hispanic whites (1.17%) and non-Hispanic blacks (1.24%) 50-59 years of age; and whites non-Hispanic (0.91%), and non-Hispanic blacks (0.96%). During 2003-2016 overall myeloma (extramedullary plasmacytoma and multiple myeloma) death rates among adults was 4.77 per 100,00 persons. Myeloma death rates decreased during 2003-2016 among non-Hispanic white (AAPC = -1.23%) and Hispanic (-1.34%) women; and non-Hispanic white (-0.74%), non-Hispanic American Indian/Alaska Native (-3.05%) men. The US population is projected to become older and will have a larger proportion of persons who have had an earlier and longer exposure to excess body weight. The potential impact of these population changes on myeloma incidence and mortality can be monitored with high-quality cancer surveillance data.

      4. BMI and blood pressure improvements with a pediatric weight management intervention at federally qualified health centersexternal icon
        Imoisili OE, Lundeen EA, Freedman DS, Womack LS, Wallace J, Hambidge SJ, Federico S, Everhart R, Harr D, Vance J, Kompaniyets L, Dooyema C, Park S, Blanck HM, Goodman AB.
        Acad Pediatr. 2020 Dec 3.
        OBJECTIVE: The Mind, Exercise, Nutrition, Do It! 7-13 (MEND 7-13) program was adapted in 2016 by five Denver Health federally qualified health centers (DH FQHC) into MEND+, integrating clinician medical visits into the curriculum and tracking health measures within an electronic health record (EHR). We examined trajectories of body mass index (BMI, kg/m(2)) percentile, and systolic and diastolic blood pressures (SBP & DBP) among MEND+ attendees in an expanded age range of 4-17 years, and comparable non-attendees. METHODS: Data from April 2015 to May 2018 were extracted from DH FQHC EHR for children eligible for MEND+ referral (BMI ≥85(th) percentile). The sample included 347 MEND+ attendees and 21,061 non-attendees. Mixed-effects models examined average rate of change for BMI percent of the 95(th) percentile (%BMIp95), SBP, and DBP, after completion of the study period. RESULTS: Most children were ages 7-13 years, half were male, and most were Hispanic. An average of 4.2 MEND+ clinical sessions were attended. Before MEND+, %BMIp95 increased by 0.247 units/month among MEND+ attendees. After attending, %BMIp95 decreased by 0.087 units/month (p<0.001). Eligible non-attendees had an increase of 0.084/month in %BMIp95. Before MEND+ attendance, SBP and DBP increased by 0.041 and 0.022/month, respectively. After MEND+ attendance, SBP and DBP decreased by 0.254 /month (p<0.001) and 0.114/month (p<0.01), respectively. SBP and DBP increased by 0.032 and 0.033/month in eligible non-attendees, respectively. CONCLUSIONS: %BMIp95, SBP, and DBP significantly decreased among MEND+ attendees when implemented in community-based clinical practice settings at DH FQHC.

      5. Examining and improving knowledge and attitudes about epilepsy has been a public health priority because of stigma around the disorder. This study had three goals: (1) to update estimates describing U.S. adults' perceived knowledge about epilepsy, seizure first aid, and confidence in providing seizure first aid; (2) to examine U.S. adults' recognition of common signs and symptoms of generalized and focal seizures to inform public awareness efforts; and (3) to provide baseline estimates of exposure to an Epilepsy Foundation public awareness campaign, #ShareMySeizure, launched in November, 2016. Four sets of epilepsy questions were included on the 2017 Porter Novelli ConsumerStyles survey, an online panel survey of the U.S. adult population. We examined differences in study outcomes by sociodemographic factors and familiarity with someone with epilepsy. Small percentages of U.S. adults felt knowledgeable about epilepsy (16%), knew seizure first aid (25%), or reported having confidence in being able to help someone having a seizure with appropriate seizure first aid (20%). Fewer adults were familiar with signs of focal seizures compared to generalized seizures. About 1% of U.S. adults had heard of the #ShareMySeizure campaign. Television and family and friends emerged as the most common sources of information for those who reported hearing something about epilepsy. About 33% of U.S. adults wanted to learn more about epilepsy. Knowledge about epilepsy among the U.S. public is suboptimal, though generally on par with that of more common conditions such as heart disease, eye conditions, and ovarian cancer. U.S. adults need and want more information about epilepsy, appropriate seizure first aid training, and recognition of seizure symptoms.

      6. Patient health utility equations for a type 2 diabetes modelexternal icon
        Neuwahl SJ, Zhang P, Chen H, Shao H, Laxy M, Anderson AM, Craven TE, Hoerger TJ.
        Diabetes Care. 2020 Dec 4.
        OBJECTIVE: To estimate the health utility impact of diabetes-related complications in a large, longitudinal U.S. sample of people with type 2 diabetes. RESEARCH DESIGN AND METHODS: We combined Health Utilities Index Mark 3 data on patients with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Look AHEAD (Action for Health in Diabetes) trials and their follow-on studies. Complications were classified as events if they occurred in the year preceding the utility measurement; otherwise, they were classified as a history of the complication. We estimated utility decrements associated with complications using a fixed-effects regression model. RESULTS: Our sample included 15,252 persons with an average follow-up of 8.2 years and a total of 128,873 person-visit observations. The largest, statistically significant (P < 0.05) health utility decrements were for stroke (event, -0.109; history, -0.051), amputation (event, -0.092; history, -0.150), congestive heart failure (event, -0.051; history, -0.041), dialysis (event, -0.039), estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m(2) (event, -0.043; history, -0.025), angina (history, -0.028), and myocardial infarction (MI) (event, -0.028). There were smaller effects for laser photocoagulation and eGFR <60 mL/min/1.73 m(2). Decrements for dialysis history, angina event, MI history, revascularization event, revascularization history, laser photocoagulation event, and hypoglycemia were not significant (P ≥ 0.05). CONCLUSIONS: With use of a large study sample and a longitudinal design, our estimated health utility scores are expected to be largely unbiased. Estimates can be used to describe the health utility impact of diabetes complications, improve cost-effectiveness models, and inform diabetes policies.

      7. Defect-free care trends in the Paul Coverdell National Acute Stroke Program, 2008-2018external icon
        Overwyk KJ, Yin X, Tong X, King SM, Wiltz JL.
        Am Heart J. 2020 Nov 27.
        BACKGROUND: In an effort to improve stroke quality of care and patient outcomes, quality of care metrics are monitored to assess utilization of evidence-based stroke care processes as part of the Paul Coverdell National Acute Stroke Program (PCNASP). We aimed to assess temporal trends in defect free care (DFC) received by stroke patients in the PCNASP between 2008 and 2018. METHODS: Quality of care data for ten performance measures were available for 849,793 patients aged ≥18 years who were admitted to a participating hospital with a clinical diagnosis of stroke between 2008 and 2018. A patient who receives care according to all performance measures for which they are eligible, receives "defect-free care" (DFC) (e.g. appropriate medications, assessments and education). Generalized estimating equations were used to examine the factors associated with receipt of DFC. RESULTS: DFC among ischemic stroke patients increased from 38.0% in 2008 to 80.8% in 2018 (p<0.0001), with the largest improvement seen in receipt of stroke education (relative percent change, RPC=64%). Similarly, DFC for hemorrhagic stroke and transient ischemic attack patients increased from 46.7% to 82.6% (RPC=76.9%) and 39.9% to 85.0% (RPC=113.0%) (p<0.001), respectively. Among ischemic stroke patients, the adjusted odds for receiving DFC were lower for women, patients aged 18-54 years, Medicaid or Medicare participants, and patients with atrial fibrillation (p<0.05). CONCLUSIONS: From 2008-2018, receipt of DFC by ischemic stroke patients significantly increased in the PCNASP; however certain subgroups were less likely to receive this level of care. Targeted quality improvement initiatives could result in even further improvements among all stroke patients and help reduce disparities in care.

      8. BACKGROUND: The Centers for Disease Control and Prevention (CDC) funds the Colorectal Cancer Control Program (CRCCP) to increase colorectal cancer (CRC) screening rates in primary care clinics by implementing evidence-based interventions (EBIs). This study examined differences in clinic characteristics and implementation efforts among clinics with differential changes in screening rates over time. METHODS: CRCCP clinic data collected by the CDC were used. The outcome was the clinic status (highest quartile [Q4] vs lowest quartile [Q1]), which was based on the absolute screening rate change between the first and second program years. Five clinic characteristic variables and 12 clinic-level CRCCP variables (eg, EBIs) were assessed in bivariable analyses, and logistic regression was used to determine significant predictors of the outcome. RESULTS: Each group included 78 clinics (N = 156). Clinics with a Q4 status saw a 14.9 percentage point increase in the screening rate, whereas clinics with a Q1 status experienced a 9.1 percentage point decline. Q4s were more likely than Q1s to have a CRC champion, implement 4 EBIs versus fewer EBIs, implement at least 1 new EBI, and increase the number of implemented EBIs. The adjusted odds of Q4 status were 5.3 times greater (95% confidence interval [CI], 1.9-14.9) if a clinic implemented an additional EBI. The adjusted odds of Q4 status increased to 7.1 (95% CI, 2.2-23.1) if a clinic implemented 2 to 4 additional EBIs. CONCLUSIONS: Implementing new EBIs or enhancing existing ones improves CRC screening rates. Additionally, clinics with lower screening rates had greater rate increases and may have benefited more from the CRCCP.

      9. Proportion of never smokers among men and women with lung cancer in 7 US statesexternal icon
        Siegel DA, Fedewa SA, Henley SJ, Pollack LA, Jemal A.
        JAMA Oncol. 2020 Dec 3.

      10. Using electronic dental records to establish a surveillance system for dental decay in rural Western Alaskaexternal icon
        Thomas TK, Lenaker D, Day GM, Wilson JC, Holck P, Newman J, Bruden D, Hennessy TW.
        J Public Health Dent. 2020 Dec 6.
        OBJECTIVES: Previous surveys have demonstrated high rates of early childhood caries (ECC) in the Alaska Native (AN) population of western Alaska. There are many challenges to providing dental care in this road-less Yukon-Kuskokwim Delta region. The regional Tribal Health Organization implemented an electronic dental record (EDR) system in the late 1990s. We explored use of the EDR to establish an oral health surveillance system in children. METHODS: We contracted with EDR software developers to implement calculation of a summary count of decayed (d), missing (m) or filled (f) primary (dmft) score for each individual. We calculated the yearly average dmft scores for 2011-2019 for children aged 3 and 5 years with a comprehensive exam in a given year. We also assessed the number of children undergoing full mouth dental rehabilitation (FMDR). We used US census data population estimates for these age groups to calculate rates. RESULTS: Over the 9-year period, 2,427 3-year-old children (47 percent of all 3-year olds over this period), received a comprehensive exam; increasing from 24 percent in 2011 to 62 percent in 2019. Their average dmft score over the 9-years was 6.4 with a significant annual decline over this period. Seventy percent of AN children who turned 6 between 2015 and 2019 had received at least one FMDR. CONCLUSIONS: An oral health surveillance system has been established in western Alaska using the Electronic Dental Record. High rates of ECC and FMDR were observed. This surveillance system will allow assessments of ECC prevalence and impact of dental interventions.

      11. Relative hypoxia and early diabetic kidney disease in type 1 diabetesexternal icon
        Vinovskis C, Li LP, Prasad P, Tommerdahl K, Pyle L, Nelson RG, Pavkov ME, van Raalte D, Rewers M, Pragnell M, Mahmud FH, Cherney DZ, Johnson RJ, Nadeau KJ, Bjornstad P.
        Diabetes. 2020 Dec;69(12):2700-2708.
        The objective of this study was to compare the ratio of renal oxygen availability (RO(2)) to glomerular filtration rate (GFR), a measure of relative renal hypoxia, in adolescents with and without type 1 diabetes (T1D) and relate the ratio to albuminuria, renal plasma flow (RPF), fat mass, and insulin sensitivity (M/I). RO(2) was estimated by blood oxygen level-dependent MRI; fat mass was estimated by DXA; GFR and RPF were estimated by iohexol and p-aminohippurate clearance; albuminuria was estimated by urine albumin-to-creatinine ratio (UACR); and M/I was estimated from steady-state glucose infusion rate/insulin (mg/kg/min) by hyperglycemic clamp in 50 adolescents with T1D (age 16.1 ± 3.0 years, HbA(1c) 8.6 ± 1.2%) and 20 control patients of similar BMI (age 16.1 ± 2.9 years, HbA(1c) 5.2 ± 0.2%). The RO(2):GFR (ms/mL/min) was calculated as RO(2) (T2*, ms) divided by GFR (mL/min). Whole-kidney RO(2):GFR was 25% lower in adolescents with T1D versus control patients (P < 0.0001). In adolescents with T1D, lower whole-kidney RO(2):GFR was associated with higher UACR (r = -0.31, P = 0.03), RPF (r = -0.52, P = 0.0009), and fat mass (r = -0.33, P = 0.02). Lower medullary RO(2):GFR was associated with lower M/I (r = 0.31, P = 0.03). In conclusion, adolescents with T1D exhibited relative renal hypoxia that was associated with albuminuria and with increased RPF, fat mass, and insulin resistance. These data suggest a potential role of renal hypoxia in the development of diabetic kidney disease.

    • Communicable Diseases
      1. COVID-19 investigational treatments in use among hospitalized patients identified through the US Coronavirus Disease 2019-Associated Hospitalization Surveillance Network, March 1-June 30, 2020external icon
        Acosta AM, Mathis AL, Budnitz DS, Geller AI, Chai SJ, Alden NB, Meek J, Anderson EJ, Ryan P, Kim S, Como-Sabetti K, Torres S, Dufort E, Bennett NM, Billing LM, Sutton M, Keipp Talbot H, George A, Pham H, Hall AJ, Fry A, Garg S, Kim L.
        Open Forum Infect Dis. 2020 Nov;7(11):ofaa528.
        Using a coronavirus disease 2019 (COVID-19)-associated hospitalization surveillance network, we found that 42.5% of hospitalized COVID-19 cases with available data from March 1-June 30, 2020, received ≥1 COVID-19 investigational treatment. Hydroxychloroquine, azithromycin, and remdesivir were used frequently; however, hydroxychloroquine and azithromycin use declined over time, while use of remdesivir increased.

      2. Diagnostic value of clinical features to distinguish enteric fever from other febrile illnesses in Bangladesh, Nepal, and Pakistanexternal icon
        Aiemjoy K, Tamrakar D, Saha S, Naga SR, Yu AT, Longley A, Date K, Hemlock C, Qamar FN, Saha SK, Luby SP, Garrett DO, Andrews JR, Bogoch .
        Clin Infect Dis. 2020 Dec 1;71(Supplement_3):S257-s265.
        BACKGROUND: Enteric fever, a bacterial infection caused by Salmonella enterica serotypes Typhi and Paratyphi A, frequently presents as a nonlocalizing febrile illness that is difficult to distinguish from other infectious causes of fever. Blood culture is not widely available in endemic settings and, even when available, results can take up to 5 days. We evaluated the diagnostic performance of clinical features, including both reported symptoms and clinical signs, of enteric fever among patients participating in the Surveillance for Enteric Fever in Asia Project (SEAP), a 3-year surveillance study in Bangladesh, Nepal, and Pakistan. METHODS: Outpatients presenting with ≥3 consecutive days of reported fever and inpatients with clinically suspected enteric fever from all 6 SEAP study hospitals were eligible to participate. We evaluated the diagnostic performance of select clinical features against blood culture results among outpatients using mixed-effect regression models with a random effect for study site hospital. We also compared the clinical features of S. Typhi to S. Paratyphi A among both outpatients and inpatients. RESULTS: We enrolled 20 899 outpatients, of whom 2116 (10.1%) had positive blood cultures for S. Typhi and 297 (1.4%) had positive cultures for S. Paratyphi A. The sensitivity of absence of cough was the highest among all evaluated features, at 65.5% (95% confidence interval [CI], 55.0-74.7), followed by measured fever at presentation at 59.0% (95% CI, 51.6-65.9) and being unable to complete normal activities for 3 or more days at 51.0% (95% CI, 23.8-77.6). A combined case definition of 3 or more consecutive days of reported fever and 1 or more of the following (a) either the absence of cough, (b) fever at presentation, or (c) 3 or more consecutive days of being unable to conduct usual activity--yielded a sensitivity of 94.6% (95% CI, 93.4-95.5) and specificity of 13.6% (95% CI, 9.8-17.5). CONCLUSIONS: Clinical features do not accurately distinguish blood culture-confirmed enteric fever from other febrile syndromes. Rapid, affordable, and accurate diagnostics are urgently needed, particularly in settings with limited or no blood culture capacity.

      3. Healthcare utilization patterns for acute febrile illness in Bangladesh, Nepal, and Pakistan: Results from the Surveillance for Enteric Fever in Asia Projectexternal icon
        Andrews JR, Vaidya K, Saha S, Yousafzai MT, Hemlock C, Longley A, Aiemjoy K, Yu AT, Bogoch , Tamrakar D, Date K, Saha SK, Garrett DO, Luby SP, Qamar F.
        Clin Infect Dis. 2020 Dec 1;71(Supplement_3):S248-s256.
        BACKGROUND: Characterizing healthcare-seeking patterns for acute febrile illness is critical for generating population-based enteric fever incidence estimates from facility-based surveillance data. METHODS: We used a hybrid model in the Surveillance for Enteric Fever in Asia Project (SEAP) to assess incidence of enteric fever at 6 study hospitals in 3 countries. We recruited individuals presenting to the hospitals and obtained blood cultures to evaluate for enteric fever. For this analysis, we undertook cluster random household surveys in Dhaka, Bangladesh (2 sites); Karachi, Pakistan; Kathmandu, Nepal; and Kavrepalanchok, Nepal between January 2017 and February 2019, to ascertain care-seeking behavior for individuals with 1) fever for ≥3 consecutive days within the past 8 weeks; or 2) fever resulting in hospitalization within the past year. We also collected data about disease severity and household demographics and assets. We used mixed-effect multivariable logistic regression models to identify determinants of healthcare seeking at study hospitals and determinants of culture-confirmed enteric fever. RESULTS: We enrolled 31 841 households (53 926 children) in Bangladesh, 25 510 households (84 196 children and adults) in Nepal, and 21 310 households (108 031 children and adults) in Pakistan. Children <5 years were most likely to be taken to the study hospitals for febrile illness at all sites. Household wealth was positively correlated with healthcare seeking in 4 of 5 study sites, and at least one marker of disease severity was positively associated with healthcare seeking in 3 of 5 catchment areas. Wealth and disease severity were variably predictive of blood culture-confirmed enteric fever. CONCLUSIONS: Age, household wealth, and disease severity are important determinants of healthcare seeking for acute febrile illness and enteric fever risk in these communities, and should be incorporated into estimation models for enteric fever incidence.

      4. Comparison of estimated SARS-CoV-2 seroprevalence through commercial laboratory residual sera testing and a community surveyexternal icon
        Bajema KL, Dahlgren FS, Lim TW, Bestul N, Biggs HM, Tate JE, Owusu C, Szablewski CM, Drenzek C, Drobeniuc J, Semenova V, Li H, Browning P, Desai R, Epperson M, Jia LT, Thornburg NJ, Edens C, Fry AM, Hall AJ, Schiffer J, Havers FP.
        Clin Infect Dis. 2020 Dec 10.
        We compared severe acute respiratory syndrome-related coronavirus-2 seroprevalence estimated from commercial laboratory residual sera and a community household survey in metropolitan Atlanta during April-May 2020 and found these two estimates to be similar (4.94% versus 3.18%). Compared with more representative surveys, commercial sera can provide an approximate measure of seroprevalence.

      5. Theory-based behavioral predictors of self-reported use of face coverings in public settings during the COVID-19 pandemic in the United Statesexternal icon
        Barile JP, Guerin RJ, Fisher KA, Tian LH, Okun AH, Vanden Esschert KL, Jeffers A, Gurbaxani BM, Thompson WW, Prue CE.
        Ann Behav Med. 2020 Dec 10.
        BACKGROUND: Investigating antecedents of behaviors, such as wearing face coverings, is critical for developing strategies to prevent SARS-CoV-2 transmission. PURPOSE: The purpose of this study was to determine associations between theory-based behavioral predictors of intention to wear a face covering and actual wearing of a face covering in public. METHODS: Data from a cross-sectional panel survey of U.S. adults conducted in May and June 2020 (N = 1,004) were used to test a theory-based behavioral path model. We (a) examined predictors of intention to wear a face covering, (b) reported use of cloth face coverings, and (c) reported use of other face masks (e.g., a surgical mask or N95 respirator) in public. RESULTS: We found that being female, perceived importance of others wanting the respondent to wear a face covering, confidence to wear a face covering, and perceived importance of personal face covering use was positively associated with intention to wear a face covering in public. Intention to wear a face covering was positively associated with self-reported wearing of a cloth face covering if other people were observed wearing cloth face coverings in public at least "rarely" (aOR = 1.43), with stronger associations if they reported "sometimes" (aOR = 1.83), "often" (aOR = 2.32), or "always" (aOR = 2.96). For other types of face masks, a positive association between intention and behavior was only present when observing others wearing face masks "often" (aOR = 1.25) or "always" (aOR = 1.48). CONCLUSIONS: Intention to wear face coverings and observing other people wearing them are important behavioral predictors of adherence to the CDC recommendation to wear face coverings in public.

      6. Travel-associated cases of Legionnaires' disease in the United States, 2015-201external icon
        Barskey AE, Lackraj D, Tripathi PS, Lee S, Smith J, Edens C.
        Travel Med Infect Dis. 2020 Dec 3:101943.
        BACKGROUND: Recent travel is associated with ∼20% of reported Legionnaires' disease (LD) cases worldwide. METHODS: We analyzed LD cases reported to the Centers for Disease Control and Prevention (CDC) during 2015-2016. Travel-associated cases met case criteria for confirmed LD in someone who spent ≥1 night away from home during the 10 days before symptom onset. Most analyses were limited to travel-associated, public accommodation stay (TAPAS) cases. We used reported travel dates to estimate the number of TAPAS cases acquired during travel. RESULTS: Of 12,200 LD cases reported among U.S. residents, 12.3% were travel-associated; 8.7% were TAPAS. Median patient age for TAPAS cases was 61 years; 64.4% were male; 67.3% were white; 77.9% were non-Hispanic; 96.1% were hospitalized; 4.5% died. Among 887 TAPAS cases involving U.S. destinations, an estimated 29.8% were acquired during travel; 4.28 TAPAS cases were reported, and an estimated 1.10 TAPAS cases were acquired during travel, per 10,000,000 hotel room nights booked. Sixty-eight U.S. TAPAS clusters were detected. CONCLUSIONS: While acquisition during travel accounted for a relatively small proportion of all LD cases, clusters of TAPAS cases were frequently detected. Prompt notification of these cases to CDC facilitates cluster detection and expedites intervention.

      7. Serologic testing of U.S. blood donations to identify SARS-CoV-2-reactive antibodies: December 2019-January 2020external icon
        Basavaraju SV, Patton ME, Grimm K, Rasheed MA, Lester S, Mills L, Stumpf M, Freeman B, Tamin A, Harcourt J, Schiffer J, Semenova V, Li H, Alston B, Ategbole M, Bolcen S, Boulay D, Browning P, Cronin L, David E, Desai R, Epperson M, Gorantla Y, Jia T, Maniatis P, Moss K, Ortiz K, Park SH, Patel P, Qin Y, Steward-Clark E, Tatum H, Vogan A, Zellner B, Drobeniuc J, Sapiano MR, Havers F, Reed C, Gerber S, Thornburg NJ, Stramer SL.
        Clin Infect Dis. 2020 Nov 30.
        BACKGROUND: SARS-CoV-2, the virus that causes COVID-19 disease, was first identified in Wuhan, China in December 2019, with subsequent worldwide spread. The first U.S. cases were identified in January 2020. METHODS: To determine if SARS-CoV-2 reactive antibodies were present in sera prior to the first identified case in the U.S. on January 19, 2020, residual archived samples from 7,389 routine blood donations collected by the American Red Cross from December 13, 2019 to January 17, 2020, from donors resident in nine states (California, Connecticut, Iowa, Massachusetts, Michigan, Oregon, Rhode Island, Washington, and Wisconsin) were tested at CDC for anti-SARS-CoV-2 antibodies. Specimens reactive by pan-immunoglobulin (pan Ig) enzyme linked immunosorbent assay (ELISA) against the full spike protein were tested by IgG and IgM ELISAs, microneutralization test, Ortho total Ig S1 ELISA, and receptor binding domain / Ace2 blocking activity assay. RESULTS: Of the 7,389 samples, 106 were reactive by pan Ig. Of these 106 specimens, 90 were available for further testing. Eighty four of 90 had neutralizing activity, 1 had S1 binding activity, and 1 had receptor binding domain / Ace2 blocking activity >50%, suggesting the presence of anti-SARS-CoV-2-reactive antibodies. Donations with reactivity occurred in all nine states. CONCLUSIONS: These findings suggest that SARS-CoV-2 may have been introduced into the United States prior to January 19, 2020.

      8. Enterovirus D68 infection among hospitalized children with severe acute respiratory illness in El Salvador and Panama, 2012-2013external icon
        Biggs HM, Nix WA, Zhang J, Rogers S, Clara W, Jara JH, Gonzalez R, Luciani K, Brizuela YS, Estripeaut D, Castillo JM, De Leon T, Corro M, Vergara O, Rauda R, Chong EG, Watson JT, Azziz-Baumgartner E, Gerber SI, Tong S, Dawood FS.
        Influenza Other Respir Viruses. 2020 Dec 5.
        We assessed EV-D68 epidemiology and phylogenetics among children aged ≤9 years hospitalized with severe acute respiratory illnesses at five sites in Panama and El Salvador during 2012-2013. Respiratory specimens positive for enterovirus or rhinovirus were tested by real-time RT-PCR for EV-D68, and partial VP1 gene sequences were determined. Of 715 enrolled children, 17 from sites in both countries were EV-D68-positive and commonly had a history of asthma or wheezing. Phylogenetically, 15 of 16 sequences fell into Clade B1, and one into Clade A2. The Central American EV-D68s were closely related genetically to contemporaneous strains from North America, South America, and the Caribbean.

      9. Handwashing and disinfection precautions taken by U.S. adults to prevent coronavirus disease 2019, Spring 2020external icon
        Brown LG, Hoover ER, Barrett CE, Vanden Esschert KL, Collier SA, Garcia-Williams AG.
        BMC Res Notes. 2020 Dec 4;13(1):550.
        OBJECTIVES: The objectives of this study were to assess self-reported hygiene precautions taken by U.S. adults during spring 2020 to prevent coronavirus disease 2019 (COVID-19) and to identify demographic characteristics associated with these hygiene precautions. RESULTS: We obtained data from Porter Novelli Public Services's national survey, Spring ConsumerStyles, conducted March 19-April 9, 2020 among a nationally representative random sample of 6463 U.S. adults aged 18 years or older. We present data from the survey question: "What, if any, precautions are you taking to prevent coronavirus?". Respondents replied yes or no to the following precautions: washing hands often with soap and water and disinfecting surfaces at home and work often. Most respondents reported taking hygiene-related precautions to prevent COVID-19; more respondents reported handwashing (93%) than disinfecting surfaces (74%). Men, younger respondents, those with lower income and education levels, and respondents in self-rated poor health had lower reported rates of both handwashing and disinfecting surfaces. Communications about hygiene precautions for COVID-19 prevention may need to target sub-populations with the greatest gaps in hygiene-related practices. Research identifying barriers to these practices and developing effective messaging could inform and improve these communications.

      10. Multidisciplinary community-based investigation of a COVID-19 outbreak among Marshallese and Hispanic/Latino communities - Benton and Washington Counties, Arkansas, March-June 2020external icon
        Center KE, Da Silva J, Hernandez AL, Vang K, Martin DW, Mazurek J, Lilo EA, Zimmerman NK, Krow-Lucal E, Campbell EM, Cowins JV, Walker C, Dominguez KL, Gallo B, Gunn JK, McCormick D, Cochran C, Smith MR, Dillaha JA, James AE.
        MMWR Morb Mortal Wkly Rep. 2020 Dec 4;69(48):1807-1811.
        By June 2020, Marshallese and Hispanic or Latino (Hispanic) persons in Benton and Washington counties of Arkansas had received a disproportionately high number of diagnoses of coronavirus disease 2019 (COVID-19). Despite representing approximately 19% of these counties' populations (1), Marshallese and Hispanic persons accounted for 64% of COVID-19 cases and 57% of COVID-19-associated deaths. Analyses of surveillance data, focus group discussions, and key-informant interviews were conducted to identify challenges and propose strategies for interrupting transmission of SARS-CoV-2, the virus that causes COVID-19. Challenges included limited native-language health messaging, high household occupancy, high employment rate in the poultry processing industry, mistrust of the medical system, and changing COVID-19 guidance. Reducing the COVID-19 incidence among communities that suffer disproportionately from COVID-19 requires strengthening the coordination of public health, health care, and community stakeholders to provide culturally and linguistically tailored public health education, community-based prevention activities, case management, care navigation, and service linkage.

      11. Implementing mitigation strategies in early care and education settings for prevention of SARS-CoV-2 transmission - eight states, September-October 2020external icon
        Coronado F, Blough S, Bergeron D, Proia K, Sauber-Schatz E, Beltran M, Rau KT, McMichael A, Fortin T, Lackey M, Rohs J, Sparrow T, Baldwin G.
        MMWR Morb Mortal Wkly Rep. 2020 Dec 11;69(49):1868-1872.
        The Head Start program, including Head Start for children aged 3-5 years and Early Head Start for infants, toddlers, and pregnant women, promotes early learning and healthy development among children aged 0-5 years whose families meet the annually adjusted Federal Poverty Guidelines* throughout the United States.(†) These programs are funded by grants administered by the U.S. Department of Health and Human Services' Administration for Children and Families (ACF). In March 2020, Congress passed the Coronavirus Aid, Relief, and Economic Security (CARES) Act,(§) which appropriated $750 million for Head Start, equating to approximately $875 in CARES Act funds per enrolled child. In response to the coronavirus disease 2019 (COVID-19) pandemic, most states required all schools (K-12) to close or transition to virtual learning. The Office of Head Start gave its local programs that remained open the flexibility to use CARES Act funds to implement CDC-recommended guidance (1) and other ancillary measures to provide in-person services in the early phases of community transmission of SARS-CoV-2, the virus that causes COVID-19, in April and May 2020, when many similar programs remained closed. Guidance included information on masks, other personal protective equipment, physical setup, supplies necessary for maintaining healthy environments and operations, and the need for additional staff members to ensure small class sizes. Head Start programs successfully implemented CDC-recommended mitigation strategies and supported other practices that helped to prevent SARS-CoV-2 transmission among children and staff members. CDC conducted a mixed-methods analysis to document these approaches and inform implementation of mitigation strategies in other child care settings. Implementing and monitoring adherence to recommended mitigation strategies reduces risk for COVID-19 transmission in child care settings. These approaches could be applied to other early care and education settings that remain open for in-person learning and potentially reduce SARS-CoV-2 transmission.

      12. The role of nurses and midwives in expanding and sustaining voluntary medical male circumcision services for HIV prevention: A systematic and policy reviewexternal icon
        Davis SM, Baker H, Gross JM, Leslie SL, Chasokela CM, Samuelson J, Toledo C.
        J Assoc Nurses AIDS Care. 2020 Dec 8.
        Male circumcision reduces men's risk of acquiring HIV through heterosexual sex, and voluntary medical male circumcision (VMMC) is central to HIV prevention strategies in 15 sub-Saharan African countries. Nurses have emerged as primary VMMC providers; however, barriers remain to institutionalizing nurse-led VMMC. Patient safety concerns have hindered task sharing, and regulations governing nurse-performed VMMC are not always supportive or clear. We performed a systematic review on VMMC safety by provider cadre and a desk review of national policies governing the VMMC roles of nurses and midwives. Also, VMMC by nurses is safe and has become standard practice. Countries had multiple policy combinations among different documents, with only one disallowing VMMC by these cadres. Countries with alignment between policies often ensured that nursing workforces were equipped with clinical competencies through national certification. Regulatory clarity and formalized certification for nurse-performed VMMC can increase program sustainability and build nursing capacity to meet other critical basic surgical needs.

      13. Sex differences in HIV testing - 20 PEPFAR-supported sub-Saharan African Countries, 2019external icon
        Drammeh B, Medley A, Dale H, De AK, Diekman S, Yee R, Aholou T, Lasry A, Auld A, Baack B, Duffus W, Shahul E, Wong V, Grillo M, Al-Samarrai T, Ally S, Nyangulu M, Nyirenda R, Olivier J, Chidarikire T, Khanyile N, Kayange AA, Rwabiyago OE, Kategile U, Bisimba J, Weber RA, Ncube G, Maguwu O, Pietersen I, Mali D, Dzinotyiweyi E, Nelson L, Bosco MJ, Dalsone K, Apolot M, Anangwe S, Soo LK, Mugambi M, Mbayiha A, Mugwaneza P, Malamba SS, Phiri A, Chisenga T, Boyd M, Temesgan C, Shimelis M, Weldegebreal T, Getachew M, Balachandra S, Eboi E, Shasha W, Doumatey N, Adjoua D, Meribe C, Gwamna J, Gado P, John-Dada I, Mukinda E, Lukusa LF, Kalenga L, Bunga S, Achyut V, Mondi J, Loeto P, Mogomotsi G, Ledikwe J, Ramphalla P, Tlhomola M, Mirembe JK, Nkwoh T, Eno L, Bonono L, Honwana N, Chicuecue N, Simbine A, Malimane I, Dube L, Mirira M, Mndzebele P, Frawley A, Cardo YM, Behel S.
        MMWR Morb Mortal Wkly Rep. 2020 Dec 4;69(48):1801-1806.
        Despite progress toward controlling the human immunodeficiency virus (HIV) epidemic, testing gaps remain, particularly among men and young persons in sub-Saharan Africa (1). This observational study used routinely collected programmatic data from 20 African countries reported to the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) from October 2018 to September 2019 to assess HIV testing coverage and case finding among adults (defined as persons aged ≥15 years). Indicators included number of HIV tests conducted, number of HIV-positive test results, and percentage positivity rate. Overall, the majority of countries reported higher HIV case finding among women than among men. However, a slightly higher percentage positivity was recorded among men (4.7%) than among women (4.1%). Provider-initiated counseling and testing (PITC) in health facilities identified approximately two thirds of all new cases, but index testing had the highest percentage positivity in all countries among both sexes. Yields from voluntary counseling and testing (VCT) and mobile testing varied by sex and by country. These findings highlight the need to identify and implement the most efficient strategies for HIV case finding in these countries to close coverage gaps. Strategies might need to be tailored for men who remain underrepresented in the majority of HIV testing programs.

      14. Risk factors for severe acute respiratory syndrome coronavirus 2 infection in homeless shelters in Chicago, Illinois-March-May, 2020external icon
        Ghinai I, Davis ES, Mayer S, Toews KA, Huggett TD, Snow-Hill N, Perez O, Hayden MK, Tehrani S, Landi AJ, Crane S, Bell E, Hermes JM, Desai K, Godbee M, Jhaveri N, Borah B, Cable T, Sami S, Nozicka L, Chang YS, Jagadish A, Chee M, Thigpen B, Llerena C, Tran M, Surabhi DM, Smith ED, Remus RG, Staszcuk R, Figueroa E, Leo P, Detmer WM, Lyon E, Carreon S, Hoferka S, Ritger KA, Jasmin W, Nagireddy P, Seo JY, Fricchione MJ, Kerins JL, Black SR, Butler LM, Howard K, McCauley M, Fraley T, Arwady MA, Gretsch S, Cunningham M, Pacilli M, Ruestow PS, Mosites E, Avery E, Longcoy J, Lynch EB, Layden JE.
        Open Forum Infect Dis. 2020 Nov;7(11):ofaa477.
        BACKGROUND: People experiencing homelessness are at increased risk of coronavirus disease 2019 (COVID-19), but little is known about specific risk factors for infection within homeless shelters. METHODS: We performed widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction testing and collected risk factor information at all homeless shelters in Chicago with at least 1 reported case of COVID-19 (n = 21). Multivariable, mixed-effects log-binomial models were built to estimate adjusted prevalence ratios (aPRs) for SARS-CoV-2 infection for both individual- and facility-level risk factors. RESULTS: During March 1 to May 1, 2020, 1717 shelter residents and staff were tested for SARS-CoV-2; 472 (27%) persons tested positive. Prevalence of infection was higher for residents (431 of 1435, 30%) than for staff (41 of 282, 15%) (prevalence ratio = 2.52; 95% confidence interval [CI], 1.78-3.58). The majority of residents with SARS-CoV-2 infection (293 of 406 with available information about symptoms, 72%) reported no symptoms at the time of specimen collection or within the following 2 weeks. Among residents, sharing a room with a large number of people was associated with increased likelihood of infection (aPR for sharing with >20 people compared with single rooms = 1.76; 95% CI, 1.11-2.80), and current smoking was associated with reduced likelihood of infection (aPR = 0.71; 95% CI, 0.60-0.85). At the facility level, a higher proportion of residents leaving and returning each day was associated with increased prevalence (aPR = 1.08; 95% CI, 1.01-1.16), whereas an increase in the number of private bathrooms was associated with reduced prevalence (aPR for 1 additional private bathroom per 100 people = 0.92; 95% CI, 0.87-0.98). CONCLUSIONS: We identified a high prevalence of SARS-CoV-2 infections in homeless shelters. Reducing the number of residents sharing dormitories might reduce the likelihood of SARS-CoV-2 infection. When community transmission is high, limiting movement of persons experiencing homelessness into and out of shelters might also be beneficial.

      15. Racial and ethnic differences in parental attitudes and concerns about school reopening during the COVID-19 pandemic - United States, July 2020external icon
        Gilbert LK, Strine TW, Szucs LE, Crawford TN, Parks SE, Barradas DT, Njai R, Ko JY.
        MMWR Morb Mortal Wkly Rep. 2020 Dec 11;69(49):1848-1852.
        In light of the disproportionate risk of hospitalization and death attributable to coronavirus disease 2019 (COVID-19) among racial and ethnic minority groups, parental attitudes and concerns regarding school reopening were assessed by race and ethnicity using data from three online CARAVAN omnibus surveys conducted during July 8-12, 2020, by ENGINE Insights.* Survey participants included 858 parents who had children and adolescents in kindergarten through grade 12 (school-aged children) living in their household. Overall, 56.5% of parents strongly or somewhat agreed that school should reopen this fall, with some differences by race/ethnicity: compared with 62.3% of non-Hispanic White (White) parents, 46.0% of non-Hispanic Black or African American (Black) parents (p = 0.007) and 50.2% of Hispanic parents (p = 0.014) agreed that school should reopen this fall. Fewer White parents (62.5%) than Hispanic (79.5%, p = 0.026) and non-Hispanic parents of other racial/ethnic groups (66.9%, p = 0.041) were supportive of a mask mandate for students and staff members. Understanding parental attitudes and concerns is critical to informing communication and messaging around COVID-19 mitigation. Families' concerns also highlight the need for flexible education plans and equitable resource provision so that youth education is not compromised.

      16. Utilization of blood culture in South Asia for the diagnosis and treatment of febrile illnessexternal icon
        Hemlock C, Luby SP, Saha S, Qamar F, Andrews JR, Saha SK, Tamrakar D, Date K, Longley AT, Garrett DO, Bogoch .
        Clin Infect Dis. 2020 Dec 1;71(Supplement_3):S266-s275.
        BACKGROUND: Blood culture is the current standard for diagnosing bacteremic illnesses, yet it is not clear how physicians in many low- and middle-income countries utilize blood culture for diagnostic purposes and to inform treatment decisions. METHODS: We screened suspected enteric fever cases from 6 hospitals in Bangladesh, Nepal, and Pakistan, and enrolled patients if blood culture was prescribed by the treating physician. We used generalized additive regression models to analyze the probability of receiving blood culture by age, and linear regression models to analyze changes by month to the proportion of febrile cases prescribed a blood culture compared with the burden of febrile illness, stratified by hospital. We used logistic regression to analyze predictors for receiving antibiotics empirically. We descriptively reviewed changes in antibiotic therapy by susceptibility patterns and coverage, stratified by country. RESULTS: We screened 30 809 outpatients resulting in 1819 enteric fever cases; 1935 additional cases were enrolled from other hospital locations. Younger outpatients were less likely to receive a blood culture. The association between the number of febrile outpatients and the proportion prescribed blood culture varied by hospital. Antibiotics prescribed empirically were associated with severity and provisional diagnoses, but 31% (1147/3754) of enteric fever cases were not covered by initial therapy; this was highest in Pakistan (50%) as many isolates were resistant to cephalosporins, which were commonly prescribed empirically. CONCLUSIONS: Understanding hospital-level communication between laboratories and physicians may improve patient care and timeliness of appropriate antibiotics, which is important considering the rise of antimicrobial resistance.

      17. Summary of guidance for public health strategies to address high levels of community transmission of SARS-CoV-2 and related deaths, December 2020external icon
        Honein MA, Christie A, Rose DA, Brooks JT, Meaney-Delman D, Cohn A, Sauber-Schatz EK, Walker A, McDonald LC, Liburd LC, Hall JE, Fry AM, Hall AJ, Gupta N, Kuhnert WL, Yoon PW, Gundlapalli AV, Beach MJ, Walke HT.
        MMWR Morb Mortal Wkly Rep. 2020 Dec 11;69(49):1860-1867.
        In the 10 months since the first confirmed case of coronavirus disease 2019 (COVID-19) was reported in the United States on January 20, 2020 (1), approximately 13.8 million cases and 272,525 deaths have been reported in the United States. On October 30, the number of new cases reported in the United States in a single day exceeded 100,000 for the first time, and by December 2 had reached a daily high of 196,227.* With colder weather, more time spent indoors, the ongoing U.S. holiday season, and silent spread of disease, with approximately 50% of transmission from asymptomatic persons (2), the United States has entered a phase of high-level transmission where a multipronged approach to implementing all evidence-based public health strategies at both the individual and community levels is essential. This summary guidance highlights critical evidence-based CDC recommendations and sustainable strategies to reduce COVID-19 transmission. These strategies include 1) universal face mask use, 2) maintaining physical distance from other persons and limiting in-person contacts, 3) avoiding nonessential indoor spaces and crowded outdoor spaces, 4) increasing testing to rapidly identify and isolate infected persons, 5) promptly identifying, quarantining, and testing close contacts of persons with known COVID-19, 6) safeguarding persons most at risk for severe illness or death from infection with SARS-CoV-2, the virus that causes COVID-19, 7) protecting essential workers with provision of adequate personal protective equipment and safe work practices, 8) postponing travel, 9) increasing room air ventilation and enhancing hand hygiene and environmental disinfection, and 10) achieving widespread availability and high community coverage with effective COVID-19 vaccines. In combination, these strategies can reduce SARS-CoV-2 transmission, long-term sequelae or disability, and death, and mitigate the pandemic's economic impact. Consistent implementation of these strategies improves health equity, preserves health care capacity, maintains the function of essential businesses, and supports the availability of in-person instruction for kindergarten through grade 12 schools and preschool. Individual persons, households, and communities should take these actions now to reduce SARS-CoV-2 transmission from its current high level. These actions will provide a bridge to a future with wide availability and high community coverage of effective vaccines, when safe return to more everyday activities in a range of settings will be possible.

      18. A tale of two viruses: Coinfections of monkeypox and varicella zoster virus in the Democratic Republic of Congoexternal icon
        Hughes CM, Liu L, Davidson WB, Radford KW, Wilkins K, Monroe B, Metcalfe MG, Likafi T, Lushima RS, Kabamba J, Nguete B, Malekani J, Pukuta E, Karhemere S, Muyembe Tamfum JJ, Wemakoy EO, Reynolds MG, Schmid DS, McCollum AM.
        Am J Trop Med Hyg. 2020 Dec 7.
        Recent enhanced monkeypox (MPX) surveillance in the Democratic Republic of Congo, where MPX is endemic, has uncovered multiple cases of MPX and varicella zoster virus (VZV) coinfections. The purpose of this study was to verify if coinfections occur and to characterize the clinical nature of these cases. Clinical, epidemiological, and laboratory results were used to investigate MPX/VZV coinfections. A coinfection was defined as a patient with at least one Orthopoxvirus/MPX-positive sample and at least one VZV-positive sample within the same disease event. Between September 2009 and April 2014, 134 of the 1,107 (12.1%) suspected MPX cases were confirmed as MPX/VZV coinfections. Coinfections were more likely to report symptoms than VZV-alone cases and less likely than MPX-alone cases. Significantly higher lesion counts were observed for coinfection cases than for VZV-alone but less than MPX-alone cases. Discernible differences in symptom and rash severity were detected for coinfection cases compared with those with MPX or VZV alone. Findings indicate infection with both MPX and VZV could modulate infection severity. Collection of multiple lesion samples allows for the opportunity to detect coinfections. As this program continues, it will be important to continue these procedures to assess variations in the proportion of coinfected cases over time.

      19. Changes to the sample design and weighting methods of a public health surveillance system to also include persons not receiving HIV medical careexternal icon
        Johnson CH, Beer L, Harding RL, Iachan R, Moyse D, Lee A, Kyle T, Chowdhury PP, Shouse RL.
        PLoS One. 2020 ;15(12):e0243351.
        OBJECTIVES: The Medical Monitoring Project (MMP) is a public health surveillance system that provides representative estimates of the experiences and behaviors of adults with diagnosed HIV in the United States. In 2015, the sample design and frame of MMP changed from a system that only included HIV patients to one that captures the experiences of persons receiving and not receiving HIV care. We describe methods investigated for calculating survey weights, the approach chosen, and the benefits of using a dynamic surveillance registry as a sampling frame. METHODS: MMP samples adults with diagnosed HIV from the National HIV Surveillance System, the HIV case surveillance registry for the United States. In the methodological study presented in this manuscript, we compared methods that account for sample design and nonresponse, including weighting class adjustment vs. propensity weighting and a single-stage nonresponse adjustment vs. sequential adjustments for noncontact and nonresponse. We investigated how best to adjust for non-coverage using surveillance data to post-stratify estimates. RESULTS: After assessing these methods, we chose as our preferred procedure weighting class adjustments and a single-stage nonresponse adjustment. Classes were constructed using variables associated with respondents' characteristics and important survey outcomes, chief among them laboratory results available from surveillance that served as a proxy for medical care. CONCLUSIONS: MMPs weighting procedures reduced sample bias by leveraging auxiliary information on medical care available from the surveillance registry sampling frame. Expanding MMPs population of focus provides important information on characteristics of persons with diagnosed HIV that complement the information provided by the surveillance registry. MMP methods can be applied to other disease registries or population-monitoring systems when more detailed information is needed for a population, with the detailed information obtained efficiently from a representative sample of the population covered by the registry.

      20. Chlamydia and gonorrhea incidence and testing among patients in the Human Immunodeficiency Virus Outpatient Study (HOPS), 2007-2017external icon
        Li J, Armon C, Palella FJ, Novak RM, Ward D, Purinton S, Durham M, Buchacz K.
        Clin Infect Dis. 2020 Nov 5;71(8):1824-1835.
        BACKGROUND: Although chlamydia (CT) and gonorrhea (GC) infections are increasing in the United States, there are limited data on their incidence, testing rates, and associated risk factors among persons living with HIV (PLWH), including by anatomic site among men who have sex with men (MSM). METHODS: We analyzed 2007-2017 medical records data from Human Immunodeficiency Virus (HIV) Outpatient Study (HOPS) participants in care at 9 HIV clinics. We calculated CT (and GC) incidence and testing rates and assessed associations with sociodemographic and clinical factors using log-linear regression. RESULTS: Among 4727 PLWH, 397 had 881 CT infections and 331 had 861 GC infections, with an incidence of 2.95 and 2.88 per 100 person-years, respectively. From 2007 to 2017, incidence and testing rates increased by approximately 3.0- and 1.9-fold for CT and GC, respectively. Multivariable factors associated with incident CT (GC) included younger age, MSM, and prior diagnoses of sexually transmitted diseases (STDs). Among 1159 MSM, 583 (50.3%) had 844 CT and 843 GC tests during 2016-2017, and 26.6% of tests were 3-site (urethra, rectum, and pharynx), yielding the highest rates of CT (GC) detection. Multivariable factors associated with CT (GC) testing included younger age, non-Hispanic/Latino black race, and having prior STDs. CONCLUSIONS: Recent CT and GC incidence and testing increased among PLWH; however, only half of MSM were tested for CT or GC during 2016-2017 and less than a third of tests were 3-site. To promote sexual health and STD prevention among PLWH who are MSM, research regarding the added value of CT and GC testing across 3 anatomic sites is needed.

      21. Illness severity and outcomes among enteric fever cases from Bangladesh, Nepal, and Pakistan: Data from the Surveillance for Enteric Fever in Asia Project, 2016-2019external icon
        Longley AT, Hemlock C, Date K, Luby SP, Andrews JR, Saha SK, Bogoch , Yousafzai MT, Garrett DO, Qamar FN.
        Clin Infect Dis. 2020 Dec 1;71(Supplement_3):S222-s231.
        BACKGROUND: Enteric fever can lead to prolonged hospital stays, clinical complications, and death. The Surveillance for Enteric Fever in Asia Project (SEAP), a prospective surveillance study, characterized the burden of enteric fever, including illness severity, in selected settings in Bangladesh, Nepal, and Pakistan. We assessed disease severity, including hospitalization, clinical complications, and death among SEAP participants. METHODS: We analyzed clinical and laboratory data from blood culture-confirmed enteric fever cases enrolled in SEAP hospitals and associated network laboratories from September 2016 to September 2019. We used hospitalization and duration of hospital stay as proxies for severity. We conducted a follow-up interview 6 weeks after enrollment to ascertain final outcomes. RESULTS: Of the 8705 blood culture-confirmed enteric fever cases enrolled, we identified 6 deaths (case-fatality ratio, .07%; 95% CI, .01-.13%), 2 from Nepal, 4 from Pakistan, and none from Bangladesh. Overall, 1.7% (90/5205) of patients recruited from SEAP hospitals experienced a clinical complication (Bangladesh, 0.6% [18/3032]; Nepal, 2.3% [12/531]; Pakistan, 3.7% [60/1642]). The most identified complications were hepatitis (n = 36), septic shock (n = 22), and pulmonary complications/pneumonia (n = 13). Across countries, 32% (2804/8669) of patients with hospitalization data available were hospitalized (Bangladesh, 27% [1295/4868]; Nepal, 29% [455/1595]; Pakistan, 48% [1054/2206]), with a median hospital stay of 5 days (IQR, 3-7). CONCLUSIONS: While defined clinical complications and deaths were uncommon at the SEAP sites, the high proportion of hospitalizations and prolonged hospital stays highlight illness severity and the need for enteric fever control measures, including the use of typhoid conjugate vaccines.

      22. Kawasaki disease and Kawasaki disease shock syndrome hospitalization rates in the United States, 2006-2018external icon
        Maddox RA, Person MK, Kennedy JL, Leung J, Abrams JY, Haberling DL, Schonberger LB, Belay ED.
        Pediatr Infect Dis J. 2020 Dec 1.
        BACKGROUND: Kawasaki disease (KD) is a febrile illness of unknown etiology. Patients with Kawasaki disease shock syndrome (KDSS) may present with clinical signs of poor perfusion and systolic hypotension in addition to typical KD features. The United States Centers for Disease Control and Prevention analyzes and interprets large hospitalization databases as a mechanism for conducting national KD surveillance. METHODS: The Kids' Inpatient Database (KID), the National (Nationwide) Inpatient Sample (NIS), and the IBM MarketScan Commercial (MSC) and MarketScan Medicaid (MSM) databases were analyzed to determine KD-associated hospitalization rates and trends from 2006 to the most recent year of available data. KD and potential KDSS hospitalizations were defined using International Classification of Disease-Clinical Modification codes. RESULTS: For the most recent year, the KD-associated hospitalization rates for children <5 years of age were 19.8 (95% CI: 17.2-22.3, KID: 2016), 19.6 (95% CI: 16.8-22.4, NIS: 2017), 19.3 (MSC: 2018), and 18.4 (MSM: 2018) per 100,000. There was no indication of an increase in KD rates over the time period. Rates of potential KDSS among children <18 years of age, ranging from 0.0 to 0.7 per 100,000, increased; coding indicated potential KDSS for approximately 2.8%-5.3% of KD hospitalizations. CONCLUSIONS: Analyses of these large, national databases produced consistent KD-associated hospitalization rates, with no increase over time detected; however, the percentage of KD hospitalizations with potential KDSS increased. Given reports of increasing incidence elsewhere and the recent identification of a novel virus-associated syndrome with possible Kawasaki-like features, continued national surveillance is important to detect changes in disease epidemiology.

      23. Typhoid fever in the US pediatric population, 1999-2015: Opportunities for improvementexternal icon
        McAteer J, Derado G, Hughes M, Bhatnagar A, Medalla F, Chatham-Stevens K, Appiah GD, Mintz E.
        Clin Infect Dis. 2020 Jul 7.
        BACKGROUND: Typhoid fever in the United States is acquired primarily through international travel by unvaccinated travelers. There is currently no typhoid vaccine licensed in the United States for use in children <2 years. METHODS: We reviewed Salmonella enterica serotype Typhi infections reported to the Centers for Disease Control and Prevention (CDC) and antimicrobial-resistance data on Typhi isolates in CDC's National Antimicrobial Resistance Monitoring System from 1999 through 2015. RESULTS: 5131 cases of typhoid fever were diagnosed and 5004 Typhi isolates tested for antimicrobial susceptibility. Among 1992 pediatric typhoid fever patients, 1616 (81%) had traveled internationally within 30 days of illness onset, 1544 (81%) of 1906 were hospitalized (median duration, 6 days; range, 0-50), and none died. Forty percent (799) were <6 years old; 12% were <2 years old. Based on age and travel destination, 1435 (83%) of 1722 pediatric patients were vaccine-eligible; only 68 (5%) of 1361 were known to be vaccinated. Of 2003 isolates tested for antimicrobial susceptibility, 1216 (61%) were fluoroquinolone-nonsusceptible, of which 272 (22%) were also resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant [MDR]). All were susceptible to ceftriaxone and azithromycin. MDR and fluoroquinolone-nonsusceptible isolates were more common in children than adults (16% vs 9%, P < .001, and 61% vs 54%, P < .001, respectively). Fluoroquinolone nonsusceptibility was more common among travel-associated than domestically acquired cases (70% vs 17%, P < .001). CONCLUSIONS: Approximately 95% of currently vaccine-eligible pediatric travelers were unvaccinated, and antimicrobial-resistant infections were common. New public health strategies are needed to improve coverage with currently licensed vaccines. Introduction of an effective pretravel typhoid vaccine for children <2 years could reduce disease burden and prevent drug-resistant infections.

      24. Typhoid and paratyphoid cost of illness in Nepal: Patient and health facility costs from the Surveillance for Enteric Fever in Asia Project IIexternal icon
        Mejia N, Abimbola T, Andrews JR, Vaidya K, Tamrakar D, Pradhan S, Shakya R, Garrett DO, Date K, Pallas SW.
        Clin Infect Dis. 2020 Dec 1;71(Supplement_3):S306-s318.
        BACKGROUND: Enteric fever is endemic in Nepal and its economic burden is unknown. The objective of this study was to estimate the cost of illness due to enteric fever (typhoid and paratyphoid) at selected sites in Nepal. METHODS: We implemented a study at 2 hospitals in Nepal to estimate the cost per case of enteric fever from the perspectives of patients, caregivers, and healthcare providers. We collected direct medical, nonmedical, and indirect costs per blood culture-confirmed case incurred by patients and their caregivers from illness onset until after enrollment and 6 weeks later. We estimated healthcare provider direct medical economic costs based on quantities and prices of resources used to diagnose and treat enteric fever, and procedure frequencies received at these facilities by enrolled patients. We collected costs in Nepalese rupees and converted them into 2018 US dollars. RESULTS: We collected patient and caregiver cost of illness information for 395 patients, with a median cost of illness per case of $59.99 (IQR, $24.04-$151.23). Median direct medical and nonmedical costs per case represented ~3.5% of annual individual labor income. From the healthcare provider perspective, the average direct medical economic cost per case was $79.80 (range, $71.54 [hospital B], $93.43 [hospital A]). CONCLUSIONS: Enteric fever can impose a considerable economic burden on patients, caregivers, and health facilities in Nepal. These new estimates of enteric fever cost of illness can improve evaluation and modeling of the costs and benefits of enteric fever-prevention measures.

      25. Typhoid and paratyphoid cost of illness in Bangladesh: Patient and health facility costs from the Surveillance for Enteric Fever in Asia Project IIexternal icon
        Mejia N, Pallas SW, Saha S, Udin J, Sayeed KM, Garrett DO, Date K, Abimbola T.
        Clin Infect Dis. 2020 Dec 1;71(Supplement_3):S293-s305.
        BACKGROUND: We conducted a cost of illness study to assess the economic burden of pediatric enteric fever (typhoid and paratyphoid) in Bangladesh. Results can inform public health policies to prevent enteric fever. METHODS: The study was conducted at 2 pediatric health facilities in Dhaka. For the patient and caregiver's perspective, we administered questionnaires on costs incurred from illness onset until the survey dates to caregivers of patients with blood culture positive cases at enrollment and 6 weeks later to estimate the direct medical, direct nonmedical, and indirect costs. From the perspective of the health care provider, we collected data on quantities and prices of resources used by the 2 hospitals to estimate the direct medical economic costs to treat a case of enteric fever. We collected costs in Bangladeshi takas and converted them into 2018 US dollars. We multiplied the unit cost per procedure by the frequency of procedures in the surveillance case cohort to calculate the average cost per case. RESULTS: Among the 1772 patients from whom we collected information, the median cost of illness per case of enteric fever from the patient and caregiver perspective was US $64.03 (IQR: US $33.90 -$173.48). Median direct medical and nonmedical costs per case were 3% of annual labor income across the sample. From the perspective of the healthcare provider, the average direct medical cost per case was US $58.64 (range: US $37.25 at Hospital B, US $73.27 at Hospital A). CONCLUSIONS: Our results show substantial economic burden of enteric fever in Bangladesh, with higher costs for patients receiving inpatient care. As antimicrobial resistance increases globally, the cost of illness could increase, due to more expensive and potent drugs required for treatment.

      26. Typhoid and paratyphoid cost of illness in Pakistan: Patient and health facility costs from the Surveillance for Enteric Fever in Asia Project IIexternal icon
        Mejia N, Qamar F, Yousafzai MT, Raza J, Garrett DO, Date K, Abimbola T, Pallas SW.
        Clin Infect Dis. 2020 Dec 1;71(Supplement_3):S319-s335.
        BACKGROUND: The objective of this study was to estimate the cost of illness from enteric fever (typhoid and paratyphoid) at selected sites in Pakistan. METHODS: We implemented a cost-of-illness study in 4 hospitals as part of the Surveillance for Enteric Fever in Asia Project (SEAP) II in Pakistan. From the patient and caregiver perspective, we collected direct medical, nonmedical, and indirect costs per case of enteric fever incurred since illness onset by phone after enrollment and 6 weeks later. From the health care provider perspective, we collected data on quantities and prices of resources used at 3 of the hospitals, to estimate the direct medical economic costs to treat a case of enteric fever. We collected costs in Pakistani rupees and converted them into 2018 US dollars. We multiplied the unit cost per procedure by the frequency of procedures in the surveillance case cohort to calculate the average cost per case. RESULTS: We collected patient and caregiver information for 1029 patients with blood culture-confirmed enteric fever or with a nontraumatic terminal ileal perforation, with a median cost of illness per case of US $196.37 (IQR, US $72.89-496.40). The median direct medical and nonmedical costs represented 8.2% of the annual labor income. From the health care provider perspective, the estimated average direct medical cost per case was US $50.88 at Hospital A, US $52.24 at Hospital B, and US $11.73 at Hospital C. CONCLUSIONS: Enteric fever can impose a considerable economic burden in Pakistan. These new estimates of the cost of illness of enteric fever can improve evaluation and modeling of the costs and benefits of enteric fever prevention and control measures, including typhoid conjugate vaccines.

      27. Time since infection and risks of future disease for individuals with Mycobacterium tuberculosis Infection in the United Statesexternal icon
        Menzies NA, Swartwood N, Testa C, Malyuta Y, Hill AN, Marks SM, Cohen T, Salomon JA.
        Epidemiology. 2021 Jan;32(1):70-78.
        BACKGROUND: Risk of tuberculosis (TB) declines over time since Mycobacterium tuberculosis infection, but progression to clinical disease is still possible decades later. In the United States, most TB cases result from the progression of latent TB infection acquired over 2 years ago. METHODS: We synthesized evidence on TB natural history and incidence trends using a transmission-dynamic model. For the 2020 US population, we estimated average time since infection and annual, cumulative, and remaining lifetime risks of progression to TB, by nativity and age. RESULTS: For a newly infected adult with no other risk factors for progression to TB, estimated rates of progression declined from 38 (95% uncertainty interval: 33, 46) to 0.38 (0.32, 0.45) per 1000 person-years between the first and 25th year since infection. Cumulative risk over 25 years from new infection was 7.9% (7.0, 8.9). In 2020, an estimated average age of individuals with prevalent infection was 62 (61, 63) for the US-born population, 55 (54, 55) for non-US-born, and 57 (56, 58) overall. Average risks of developing TB over the remaining lifetime were 1.2% (1.0, 1.4) for US-born, 2.2% (1.8, 2.6) for non-US-born, and 1.9% (1.6, 2.2) for the general population. Risk estimates were higher for younger age groups. CONCLUSIONS: Our analysis suggests that, although newly infected individuals face appreciable lifetime TB risks, most US individuals with latent TB infection were infected long ago, and face low future risks of developing TB. Better approaches are needed for identifying recently infected individuals and those with elevated progression risks.

      28. Adult medical emergency unit presentations due to adverse drug reactions in a setting of high HIV prevalenceexternal icon
        Mouton JP, Jobanputra N, Njuguna C, Gunter H, Stewart A, Mehta U, Lahri S, Court R, Igumbor E, Maartens G, Cohen K.
        Afr J Emerg Med. 2020 .
        Introduction: South Africa has the world's largest antiretroviral treatment programme, which may contribute to the adverse drug reaction (ADR) burden. We aimed to determine the proportion of adult non-trauma emergency unit (EU) presentations attributable to ADRs and to characterise ADR-related EU presentations, stratified according to HIV status, to determine the contribution of drugs used in management of HIV and its complications to ADR-related EU presentations, and identify factors associated with ADR-related EU presentation. Methods: We conducted a retrospective folder review on a random 1.7% sample of presentations over a 12-month period in 2014/2015 to the EUs of two hospitals in Cape Town, South Africa. We identified potential ADRs with the help of a trigger tool. A multidisciplinary panel assessed potential ADRs for causality, severity, and preventability. Results: We included 1010 EU presentations and assessed 80/1010 (7.9%) as ADR-related, including 20/239 (8.4%) presentations among HIV-positive attendees. Among HIV-positive EU attendees with ADRs 17/20 (85%) were admitted, versus 22/60 (37%) of HIV-negative/unknown EU attendees. Only 5/21 (24%) ADRs in HIV-positive EU attendees were preventable, versus 24/63 (38%) in HIV-negative/unknown EU attendees. On multivariate analysis, only increasing drug count was associated with ADR-related EU presentation (adjusted odds ratio 1.10 per additional drug, 95% confidence interval 1.03 to 1.18), adjusted for age, sex, HIV status, comorbidity, and hospital. Conclusions: ADRs caused a significant proportion of EU presentations, similar to findings from other resource-limited settings. The spectrum of ADR manifestations in our EUs reflects South Africa's colliding epidemics of infectious and non-communicable diseases. ADRs among HIV-positive EU attendees were more severe and less likely to be preventable.

      29. Characteristics of adults aged 18-49 years without underlying conditions hospitalized with laboratory-confirmed COVID-19 in the United States, COVID-NET - March-August 2020external icon
        Owusu D, Kim L, O'Halloran A, Whitaker M, Piasecki AM, Reingold A, Alden NB, Maslar A, Anderson EJ, Ryan PA, Kim S, Como-Sabetti K, Hancock EB, Muse A, Bennett NM, Billing LM, Sutton M, Talbot K, Ortega J, Brammer L, Fry AM, Hall AJ, Garg S.
        Clin Infect Dis. 2020 Dec 3.
        Among 513 adults aged 18-49 years without underlying medical conditions hospitalized with COVID-19 during March-August 2020, 22% were admitted to intensive care unit; 10% required mechanical ventilation; and three patients died (0.6%). These data demonstrate that healthy younger adults can develop severe COVID-19.

      30. High coverage of antiretroviral treatment with annual home-based HIV testing, follow-up linkage services, and implementation of test and start: Findings from the Chókwè Health Demographic Surveillance System, Mozambique, 2014-2019external icon
        Pathmanathan I, Nelson R, de Louvado A, Thompson R, Pals S, Casavant I, Antonio Cardoso MJ, Ujamaa D, Bonzela J, Mikusova S, Chivurre V, Tamele S, Sleeman K, Zhang G, Zeh C, Dobbs T, Vubil A, Auld A, Briggs-Hagen M, Vergara A, Couto A, MacKellar D.
        J Acquir Immune Defic Syndr. 2020 Nov 21.
        BACKGROUND: Early antiretroviral therapy (ART) is necessary for HIV epidemic control and depends on early diagnosis and successful linkage to care. Since 2014, annual household-based HIV testing and counselling (HBHTC) and linkage services have been provided through the Chókwè Health and Demographic Surveillance System (CHDSS) for residents testing HIV-positive in this high HIV-burden district. METHODS: District-wide Test and Start (T&S, ART for all people living with HIV [PLHIV]) began in August 2016, supported by systematic interventions to improve linkage to care and treatment. Annual rounds (R) of random household surveys were conducted to assess trends in population prevalence of ART use and viral load suppression (VLS; <1000 viral RNA copies/mL). RESULTS: Between R1 (April 2014-April 2015) and R5 (April 2018-Mar 2019), 46,090 (67.2%) of 68,620 residents aged 15-59 years were tested for HIV at home at least once, and 3,711 were newly diagnosed with HIV and provided linkage services. Population prevalence of current ART use among PLHIV increased from 65.0% to 87.5% between R1 and R5. ART population prevalence was lowest among men aged 25-34 (67.8%) and women 15-24 (78.0%) years, and highest among women aged 35-44 (93.6%) and 45-59 years (93.7%) in R5. VLS prevalence increased among all PLHIV aged 15-59 years from 52.0% in R1 to 78.3% in R5. DISCUSSION: Between 2014 and 2019, CHDSS residents surpassed the UNAIDS targets of 81% of PLHIV on ART and of those, ≥73% virally suppressed. This achievement supports the combination of efforts from HBHTC, support for linkage to care and treatment, and continued investments in T&S implementation.

      31. Antimicrobial resistance in typhoidal Salmonella: Surveillance for enteric fever in Asia Project, 2016-2019external icon
        Qamar FN, Yousafzai MT, Dehraj IF, Shakoor S, Irfan S, Hotwani A, Hunzai MJ, Thobani RS, Rahman N, Mehmood J, Hemlock C, Memon AM, Andrews JR, Luby SP, Garrett DO, Longley AT, Date K, Saha SK.
        Clin Infect Dis. 2020 Dec 1;71(Supplement_3):S276-s284.
        BACKGROUND: Clinicians have limited therapeutic options for enteric as a result of increasing antimicrobial resistance, and therefore typhoid vaccination is recommended as a preventive measure. As a part of the Surveillance for Enteric Fever in Asia Project (SEAP), we investigated the extent measured the burden of antimicrobial resistance (AMR) among confirmed enteric fever cases in Bangladesh, Nepal, and Pakistan. METHODS: From September 2016-September 2019, SEAP recruited study participants of all age groups from its outpatient, inpatient, hospital laboratory, laboratory network, and surgical sites who had a diagnosis of febrile illness that was either suspected or blood culture confirmed for enteric fever. Antimicrobial resistance of isolates was determined by disc diffusion using Clinical and Laboratory Standard Institute cut-off points. We reported the frequency of multidrug resistance (MDR)(resistance to ampicillin, cotrimoxazole, and chloramphenicol), extensive drug resistance (XDR) (MDR plus non-susceptible to fluoroquinolone and any 3rd generation cephalosporins), and fluoroquinolone (FQ) and azithromycin non-susceptibility. RESULTS: We enrolled 8,705 blood culture confirmed enteric fever cases: 4,873 (56%) from Bangladesh, 1,602 (18%) from Nepal and 2,230 (26%) from Pakistan. Of these, 7,591 (87%) were Salmonella Typhi and 1114 (13%) were S. Paratyphi. MDR S. Typhi was identified in 17% (701/4065) of isolates in Bangladesh, and 1% (19/1342) in Nepal. In Pakistan, 16 % (331/2084) of S. Typhi isolates were MDR, and 64% (1319/2074) were XDR. FQ nonsusceptibility among S. Typhi isolates was 98% in Bangladesh, 87% in Nepal, and 95% in Pakistan. Azithromycin non-susceptibility was detected in 77 (2%) in Bangladesh, 9 (.67%) in Nepal and 9 (.59%) isolates in Pakistan. In Pakistan, three (2%) S. Paratyphi isolates were MDR; no MDR S. Paratyphi was reported from Bangladesh or Nepal. CONCLUSIONS: Although AMR against S. Paratyphi was low across the three countries, there was widespread drug resistance among S. Typhi, including FQ non-susceptibility and the emergence of XDR S. Typhi in Pakistan, limiting treatment options. As typhoid conjugate vaccine (TCV) is rolled out, surveillance should continue to monitor changes in AMR to inform policies and to monitor drug resistance in S. Paratyphi, for which there is no vaccine.

      32. Variability in published rates of influenza-associated hospitalizations: A systematic review, 2007-2018external icon
        Roguski KM, Rolfes MA, Reich JS, Owens Z, Patel N, Fitzner J, Cozza V, Lafond KE, Azziz-Baumgartner E, Iuliano AD.
        J Glob Health. 2020 Dec;10(2):020430.
        BACKGROUND: Influenza burden estimates help provide evidence to support influenza prevention and control programs at local and international levels. METHODS: Through a systematic review, we aimed to identify all published articles estimating rates of influenza-associated hospitalizations, describe methods and data sources used, and identify regions of the world where estimates are still lacking. We evaluated study heterogeneity to determine if we could pool published rates to generate global estimates of influenza-associated hospitalization. RESULTS: We identified 98 published articles estimating influenza-associated hospitalization rates from 2007-2018. Most articles (65%) identified were from high-income countries, with 34 of those (53%) presenting estimates from the United States. While we identified fewer publications (18%) from low- and lower-middle-income countries, 50% of those were published from 2015-2018, suggesting an increase in publications from lower-income countries in recent years. Eighty percent (n = 78) used a multiplier approach. Regression modelling techniques were only used with data from upper-middle or high-income countries where hospital administrative data was available. We identified variability in the methods, case definitions, and data sources used, including 91 different age groups and 11 different categories of case definitions. Due to the high observed heterogeneity across articles (I(2) >99%), we were unable to pool published estimates. CONCLUSIONS: The variety of methods, data sources, and case definitions adapted locally suggests that the current literature cannot be synthesized to generate global estimates of influenza-associated hospitalization burden.

      33. Evaluation of the uptake of tuberculosis preventative therapy for people living with HIV in Namibia: a multiple methods analysisexternal icon
        Roscoe C, Lockhart C, de Klerk M, Baughman A, Agolory S, Gawanab M, Menzies H, Jonas A, Salomo N, Taffa N, Lowrance D, Robsky K, Tollefson D, Pevzner E, Hamunime N, Mavhunga F, Mungunda H.
        BMC Public Health. 2020 Dec 1;20(1):1838.
        BACKGROUND: In 2016, Namibia had ~ 230,000 people living with HIV (PLHIV) and 9154 new tuberculosis (TB) cases, including 3410 (38%) co-infected cases. TB preventative therapy (TPT), consisting of intensive case finding and isoniazid preventative therapy, is critical to reducing TB disease and mortality. METHODS: Between November 2014 and February 2015, data was abstracted from charts of PLHIV enrolled in HIV treatment. Fifty-five facilities were purposively selected based on patient volume, type and location. Charts were randomly sampled. The primary outcome was to estimate baseline TPT in PLHIV, using nationally weighted proportions. Qualitative surveys were conducted and summarized to evaluate TPT practices and quantify challenges encountered by health care workers (HCW). RESULTS: Among 861 PLHIV sampled, 96% were eligible for TPT services, of which 87.1% were screened for TB at least once. For PLHIV eligible for preventative therapy (646/810; 82.6%), 45.4% (294/646) initiated therapy and 45.7% (139/294) of those completed therapy. The proportion of eligible PLHIV completing TB screening, initiating preventative therapy and then completing preventative therapy was 20.7%. Qualitative surveys with 271 HCW identified barriers to TPT implementation including: lack of training (61.3% reported receiving training on TPT); misunderstandings about timing of TPT initiation (46.7% correctly reported TPT should be started with antiretroviral therapy); and variable screening practices and responsibilities (66.1% of HCWs screened for TB at every encounter). Though barriers were evident, 72.2% HCWs surveyed described their clinical performance as very good, often placing responsibility of difficulties on patients and downplaying challenges like staff shortages and medication stock outs. CONCLUSIONS: In this study, only 1 in 5 eligible PLHIV completed the TPT cascade in Namibia. Lack of training, irregularities with TB screening and timing of TPT, unclear prescribing and recording responsibilities, and a clinical misperception may have contributed to suboptimal programmatic implementation. Addressing these challenges will be critical with continued TPT scale-up.

      34. Hospital-based surveillance for pediatric norovirus gastroenteritis in Bangladesh, 2012-2016external icon
        Satter SM, Abdullah Z, Cardemil CV, Flora MS, Gurley ES, Rahman M, Talha M, Islam MD, Hossain ME, Balachandran N, Lopman B, Rahman M, Vinjé J, Hall AJ, Parashar UD.
        Pediatr Infect Dis J. 2020 Dec 1.
        BACKGROUND: Globally, noroviruses are recognized as an important cause of acute gastroenteritis (AGE), but data from low and middle-income countries are limited. AIMS: To examine the epidemiology and strain diversity of norovirus infections among children hospitalized for AGE in Bangladesh. METHODS: We implemented active surveillance of children <5 years of age hospitalized with AGE at 8 geographically dispersed tertiary care hospitals in Bangladesh from July 2012 to June 2016. We tested random samples of AGE cases stratified by site and age group for norovirus by real-time RT-PCR. Noro-positive specimens were genotyped. Coinfection with rotavirus was assessed based on prior EIA testing. RESULTS: We enrolled 5622 total AGE cases, of which 1008 were tested for norovirus. Total of 137 (14%) AGE cases tested positive for norovirus (range, 11%-17% by site). Most (94%) norovirus-associated hospitalizations were among children less than 2 years of age. Norovirus was detected year-round, with higher detection from March to June (20%-38%) and November to January (9%-18%). Genogroup II (GII) noroviruses were detected in 96% of cases, and the most frequent genotypes were GII.4 Sydney [P4 New Orleans] (33%), GII.3 [P16] (20%), and GII.4 Sydney [P16] (11%). The proportion of norovirus-positive specimens was significantly greater among rotavirus-negative AGE patients compared with rotavirus-positive AGE patients (27% vs. 5%, P < 0.001). As measured by the Vesikari severity score, a similar proportion of norovirus and rotavirus positive AGE patients were considered severe (68% vs. 70%, P = 0.86). CONCLUSIONS: Norovirus is an important cause of AGE hospitalization in Bangladeshi children with most infections caused by GII viruses.

      35. Incidence of campylobacter-associated Guillain-Barré syndrome estimated from health insurance dataexternal icon
        Scallan Walter EJ, Crim SM, Bruce BB, Griffin PM.
        Foodborne Pathog Dis. 2020 Jan;17(1):23-28.
        Guillain-Barré syndrome (GBS) is sometimes preceded by Campylobacter infection. We estimated the cumulative incidence of Campylobacter-associated GBS in the United States using a retrospective cohort design. We identified a cohort of patients with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code of "intestinal infection due to Campylobacter" (008.43) using MarketScan Research Databases for 2004-2013. Campylobacter patients with an encounter for "acute infective polyneuritis" (AIP; ICD-9-CM 357.0) were identified. Patients with an inpatient encounter having AIP as the principal diagnosis were considered probable GBS cases. Patients with probable GBS ≤8 weeks after the Campylobacter encounter were considered probable Campylobacter-associated GBS cases. For comparison, we repeated this analysis for patients with "other Salmonella infections" (ICD-9-CM: 003). Among 9315 Campylobacter patients, 16 met the case definition for probable GBS. Two were hospitalized with probable GBS ≤8 weeks after the encounter listing a Campylobacter diagnosis (9 and 54 days) and were considered probable cases of Campylobacter-associated GBS; this results in an estimated cumulative incidence of 21.5 per 100,000 Campylobacter patients (95% confidence interval [CI]: 3.7-86.6), or 5% of all estimated GBS cases. The remaining 14 patients were diagnosed with probable GBS on the same encounter (n = 12) or 1-3 days (n = 2), before the encounter listing the Campylobacter diagnosis. Including these cases increased the cumulative incidence to 172 per 100,000 Campylobacter cases (95% CI: 101.7-285.5), 41% of estimated GBS cases. This study, using a method not previously applied to United States data, supports other data that Campylobacter is an important contributor to GBS, accounting for at least 5% and possibly as many as 41% of all GBS cases. These data can be used to inform estimates of the burden of Campylobacter infections, including economic cost.

      36. A population-based intervention to improve care cascades of patients with hepatitis C virus infectionexternal icon
        Scott J, Fagalde M, Baer A, Glick S, Barash E, Armstrong H, Kowdley KV, Golden MR, Millman AJ, Nelson NP, Canary L, Messerschmidt M, Patel P, Ninburg M, Duchin J.
        Hepatol Commun. 2020 .
        Hepatitis C virus (HCV) infection is common in the United States and leads to significant morbidity, mortality, and economic costs. Simplified screening recommendations and highly effective direct-acting antivirals for HCV present an opportunity to eliminate HCV. The objective of this study was to increase testing, linkage to care, treatment, and cure of HCV. This was an observational, prospective, population-based intervention program carried out between September 2014 and September 2018 and performed in three community health centers, three large multiclinic health care systems, and an HCV patient education and advocacy group in King County, WA. There were 232,214 patients included based on criteria of documented HCV-related diagnosis code, positive HCV laboratory test or prescription of HCV medication, and seen at least once at a participating clinical site in the prior year. Electronic health record (EHR) prompts and reports were created. Case management linked patients to care. Primary care providers received training through classroom didactics, an online curriculum, specialty clinic shadowing, and a telemedicine program. The proportion of baby boomer patients with documentation of HCV testing increased from 18% to 54% during the project period. Of 77,577 baby boomer patients screened at 87 partner clinics, 2,401 (3%) were newly identified HCV antibody positive. The number of patients staged for treatment increased by 391%, and those treated increased by 1,263%. Among the 79% of patients tested after treatment, 95% achieved sustained virologic response. Conclusion(s): A combination of EHR-based health care system interventions, active linkage to care, and clinician training contributed to a tripling in the number of patients screened and a more than 10-fold increase of those treated. The interventions are scalable and foundational to the goal of HCV elimination.

      37. Ending deaths from HIV-related cryptococcal meningitis by 2030external icon
        Shroufi A, Chiller T, Jordan A, Denning DW, Harrison TS, Govender NP, Loyse A, Baptiste S, Rajasingham R, Boulware DR, Ribeiro I, Jarvis JN, Van Cutsem G.
        Lancet Infect Dis. 2020 Nov 27.

      38. Identification of an HIV-1 and neurosyphilis cluster in Vermontexternal icon
        Singh D, Switzer WM, Belcher R, Daltry D, Read JS.
        Clin Infect Dis. 2020 Dec 8.
        BACKGROUND: Rates of syphilis in the U.S. have more than doubled over the last several decades, largely among men who have sex with men (MSM). Our study characterizes a cluster of neurosyphilis cases among HIV-1-infected individuals in Vermont in 2017-2018. METHODS: Vermont Department of Health disease intervention specialists conduct interviews with all newly diagnosed HIV-1 cases and pursued sexual networking analyses. Phylogenetic and network analyses of available Vermont HIV-1 polymerase (pol) sequences identified clusters of infection. Fishers-exact and independent t-tests were used to compare HIV-1-infected individuals within or outside an identified cluster. RESULTS: Between January 1, 2017 and December 31, 2018, 38 Vermont residents were newly diagnosed with HIV-1 infection. The mean age was 35.5 years, 79% were male and 82% were white. Risk factors for HIV-1 acquisition included MSM status (79%) and methamphetamine use (21%). Eighteen cases (49%) had HIV-1 viral loads (VLs) >100,000 copies/mL and 47% had CD4 cell counts <200/mm 3. Eleven of the 38 (29%) cases had positive syphilis serology, including four (36%) with neurosyphilis. Sexual networking analysis revealed a ten-person cluster with higher VLs at diagnosis (90% with VLs > 100,000 copies/mL vs. 33%, p=0.015). Phylogenetic analysis of pol sequences showed a cluster of 14 cases with sequences that shared 98-100% HIV-1 nucleotide identity. CONCLUSIONS: This investigation of newly infected HIV-1 cases in Vermont led to identification of a cluster that appeared more likely to have advanced HIV-1 disease and neurosyphilis. Identification of a cluster was strongly supported by both phylogenetic and network analyses of HIV-1 pol sequences.

      39. An influenza A(H3N2) virus outbreak during the COVID-19 pandemic, Kingdom of Cambodia, 2020external icon
        Sovann L, Sar B, Kab V, Yann S, Kinzer M, Raftery P, Albalak R, Patel S, Long Hay P, Seng H, Um S, Chin S, Chau D, Khalakdina A, Karlsson E, Olsen SJ, Mott JA.
        Int J Infect Dis. 2020 Nov 26.
        BACKGROUND: Coinciding with the COVID-19 pandemic, global influenza virus circulation decreased, possibly due to widespread community mitigation measures. Cambodia eased some COVID-19 mitigation measures in June and July 2020. On Aug 20th a cluster of respiratory illnesses among residents of a pagoda included persons that had tested positive for influenza A, and none that were positive for SARS-CoV-2. METHODS: On Aug 25, a response team deployed. Persons with influenza-like illness (ILI) were asked questions on demographics, illness, personal prevention measures, and residential arrangements. Respiratory swabs were tested for influenza and SARS-Cov-2 by RT-PCR; viruses were sequenced. Sentinel surveillance data were analyzed to assess recent trends in influenza circulation in the community. RESULTS: Influenza A(H3N2) viruses were identified in sentinel surveillance in Cambodia in July 2020, prior to the reported pagoda outbreak. Among the 362 pagoda residents, 73(20.2%) ILI cases were identified; 40 were tested with 33/40 (82.5%) confirmed positive for influenza A(H3N2). All 40 were negative for SARS-CoV-2. Among 73 residents with ILI, none were vaccinated against influenza, 47 (64%) clustered in 3 of 8 sleeping quarters; 20 (27%) reported often wearing a mask; 27 (36%) reported often washing hands; and 11 (15%) reported practicing social distancing. All viruses clustered within clade 3c2.A1 close to strains circulating in Australia in 2020. CONCLUSIONS: Circulation of influenza viruses began in the community following a relaxing of national COVID-19 mitigation measures, and prior to this outbreak in a pagoda with limited social distancing. Continued surveillance and influenza vaccination remain needed to limit the impact of influenza globally.

      40. Psychosocial obstacles to hepatitis C treatment initiation among patients in care: A hitch in the cascade of cureexternal icon
        Spradling PR, Zhong Y, Moorman AC, Rupp LB, Lu M, Gordon SC, Teshale EH, Schmidt MA, Daida YG, Boscarino JA.
        Hepatol Commun. 2020 .
        There are limited data examining the relationship between psychosocial factors and receipt of direct-acting antiviral (DAA) treatment among patients with hepatitis C in large health care organizations in the United States. We therefore sought to determine whether such factors were associated with DAA initiation. We analyzed data from an extensive psychological, behavioral, and social survey (that incorporated several health-related quality of life assessments) coupled with clinical data from electronic health records of patients with hepatitis C enrolled at four health care organizations during 2017-2018. Of 2,681 patients invited, 1,051 (39.2%) responded to the survey; of 894 respondents eligible for analysis, 690 (77.2%) initiated DAAs. Mean follow-up among respondents was 9.2 years. Compared with DAA recipients, nonrecipients had significantly poorer standardized scores for depression, anxiety, and life-related stressors as well as poorer scores related to physical and mental function. Lower odds of DAA initiation in multivariable analysis (adjusted by age, race, sex, study site, payment provider, cirrhosis status, comorbidity status, and duration of follow-up) included Black race (adjusted odds ratio [aOR], 0.59 vs. White race), perceived difficulty getting medical care in the preceding year (aOR, 0.48 vs. no difficulty), recent injection drug use (aOR, 0.11 vs. none), alcohol use disorder (aOR, 0.58 vs. no alcohol use disorder), severe depression (aOR, 0.42 vs. no depression), recent homelessness (aOR, 0.36 vs. no homelessness), and recent incarceration (aOR, 0.34 vs. no incarceration). Conclusion(s): In addition to racial differences, compared with respondents who initiated DAAs, those who did not were more likely to have several psychological, behavioral, and social impairments. Psychosocial barriers to DAA initiation among patients in care should also be addressed to reduce hepatitis C-related morbidity and mortality.

      41. Spatial heterogeneity of enteric fever in 2 diverse communities in Nepalexternal icon
        Tamrakar D, Vaidya K, Yu AT, Aiemjoy K, Naga SR, Cao Y, Bern C, Shrestha R, Karmacharya BM, Pradhan S, Qamar FN, Saha S, Date K, Longley AT, Hemlock C, Luby S, Garrett DO, Bogoch , Andrews JR.
        Clin Infect Dis. 2020 Dec 1;71(Supplement_3):S205-s213.
        BACKGROUND: Typhoid fever is endemic in the urban Kathmandu Valley of Nepal; however, there have been no population-based studies of typhoid outside of this community in the past 3 decades. Whether typhoid immunization should be prioritized in periurban and rural communities has been unclear. METHODS: We performed population-based surveillance for enteric fever in 1 urban catchment (Kathmandu) and 1 periurban and rural catchment (Kavrepalanchok) as part of the Surveillance for Enteric Fever in Asia Project (SEAP). We recruited individuals presenting to outpatient and emergency departments at 2 study hospitals with suspected enteric fever and performed blood cultures. Additionally, we conducted a household survey in each catchment area to characterize care seeking for febrile illness. We evaluated spatial heterogeneity in febrile illness, care seeking, and enteric fever incidence. RESULTS: Between September 2016 and September 2019, we enrolled 5736 participants with suspected enteric fever at 2 study hospitals. Among these, 304 (5.3%) were culture positive for Salmonella Typhi (249 [81.9%]) or Paratyphi A (55 [18.1%]). Adjusted typhoid incidence in Kathmandu was 484 per 100 000 person-years and in Kavrepalanchok was 615 per 100 000 person-years. While all geographic areas for which estimates could be made had incidence >200 per 100 000 person-years, we observed spatial heterogeneity with up to 10-fold variation in incidence between communities. CONCLUSIONS: In urban, periurban, and rural communities in and around Kathmandu, we measured a high but heterogenous incidence of typhoid. These findings provide some support for the introduction of conjugate vaccines in Nepal, including outside urban areas, alongside other measures to prevent enteric fever.

      42. BACKGROUND: There is a lack of information about high risk sexual behaviors (HRSB) related to gender of sex partner and associated STI/HIV testing among Medicaid enrollees. METHODS: We used the 2016 CMS Medicaid claims data to identify enrollees aged 15-60 years with HRSB by ICD-10 codes (Z72.51, Z72.52, and Z72.53). Enrollees diagnosed with HRSB were classified into two groups:1) with same-sex partners and 2) with opposite-sex partners. The date when the initial diagnosis for HRSB was documented was used to define as the index date. We assessed chlamydia, gonorrhea, syphilis, and HIV testing on the index date, in the 6-month period before and after the index date (excluded the index date). HIV testing was limited to enrollees without documented HIV infection. RESULTS: Of 50 million Medicaid enrollees aged 15-60 years, 1.2% were identified as enrollees with HRSB in 2016. Of those enrollees with HRSB, 2.7% were enrollees with same-sex partners and 0.71% had documented HIV infection. Chlamydia, gonorrhea, syphilis, and HIV testing rates were 82.4%, 81.9%, 33.2%, and 44.3%, respectively, at the index date. The chlamydia testing rate was ≥ 90% among enrollees who resided in the West, compared to 53% to 61% across other regions. HIV testing was more likely among males and among those with same-sex partners. STI/HIV testing was <30% in the 6-month periods before and after the index date. CONCLUSIONS: Among Medicaid enrollees with HRSB, STI/HIV testing varied regionally. Many enrollees were not tested for STI/HIV at the index visit in which they were identified as HRSB.

      43. Antibiotic use prior to hospital presentation among individuals with suspected enteric fever in Nepal, Bangladesh, and Pakistanexternal icon
        Vaidya K, Aiemjoy K, Qamar FN, Saha SK, Tamrakar D, Naga SR, Saha S, Hemlock C, Longley AT, Date K, Bogoch , Garrett DO, Luby SP, Andrews JR.
        Clin Infect Dis. 2020 Dec 1;71(Supplement_3):S285-s292.
        BACKGROUND: Antibiotic use prior to seeking care at a hospital may reduce the sensitivity of blood culture for enteric fever, with implications for both clinical care and surveillance. The Surveillance for Enteric Fever in Asia Project (SEAP) is a prospective study of enteric fever incidence in Nepal, Bangladesh, and Pakistan. Nested within SEAP, we evaluated the accuracy of self-reported antibiotic use and investigated the association between antibiotic use and blood culture positivity. METHODS: Between November 2016 and April 2019, we collected urine samples among a subset of SEAP participants to test for antibiotic use prior to the hospital visit using an antibacterial activity assay. All participants were asked about recent antibiotic use and had a blood culture performed. We used mixed-effect logit models to evaluate the effect of antimicrobial use on blood culture positivity, adjusted for markers of disease severity. RESULTS: We enrolled 2939 patients with suspected enteric fever. Antibiotics were detected in 39% (1145/2939) of urine samples. The correlation between measured and reported antibiotic use was modest (κ = 0.72). After adjusting for disease severity, patients with antibiotics in their urine were slightly more likely to be blood culture positive for enteric fever; however, the effect was not statistically significant (prevalence ratio, 1.22 [95% confidence interval, .99-1.50]). CONCLUSIONS: The reliability of self-reported prior antibiotic use was modest among individuals presenting with fever to tertiary hospitals. While antibiotics are likely to reduce the sensitivity of blood culture, our findings indicate that there is still considerable value in performing blood culture for individuals reporting antibiotic use.

      44. Identification of presymptomatic and asymptomatic cases using cohort-based testing approaches at a large correctional facility - Chicago, Illinois, USA, May 2020external icon
        Wadhwa A, Fisher KA, Silver R, Koh M, Arons MM, Miller DA, McIntyre AF, Vuong JT, Kim K, Takamiya M, Binder AM, Tate JE, Armstrong PA, Black SR, Mennella CC, Levin R, Gubser J, Jones B, Welbel SF, Moonan PK, Curran K, Ghinai I, Doshi R, Zawitz CJ.
        Clin Infect Dis. 2020 Dec 3.
        BACKGROUND: COVID-19 continues to cause significant morbidity and mortality worldwide. Correctional and detention facilities are at high risk of experiencing outbreaks. We aimed to evaluate cohort-based testing among detained persons exposed to laboratory-confirmed cases of SARS-CoV-2 in order to identify presymptomatic and asymptomatic cases. METHODS: During May 1-19, 2020, two testing strategies were implemented in 12 tiers or housing units of the Cook County Jail in Chicago, Illinois. Detained persons were approached to participate in serial testing (n=137) tests at 3 time points over 14 days (day 1, day 3-5, and day 13-14). The second group was offered a single test and interview at the end of a 14-day quarantine period (day 14 group) (n=87). RESULTS: A total of 224 detained persons were approached for participation and of these 194 (87%) participated in at least one interview, and 172 (77%) had at least one test. Of the 172 tested, 19 were positive for SARS-CoV-2. In the serial testing group, 17 (89%) new cases were detected, sixteen (84%) on day 1, one (5%) on days 3-5, and none on days 13-14; and, in day 14 group, two (11%) cases were identified. More than half (12/19; 63%) of the newly identified cases were pre-symptomatic or asymptomatic. CONCLUSION: Our findings highlight the utility of cohort-based testing promptly after initiating quarantine within a housing tier. Cohort-based testing efforts identified new SARS-CoV-2 asymptomatic and presymptomatic infections that may have been missed by symptom screening alone.

      45. Investigation of a large diphtheria outbreak and co-circulation of Corynebacterium pseudodiphtheriticum among forcibly displaced Myanmar nationals, 2017-2019external icon
        Weil LM, Williams MM, Shirin T, Lawrence M, Habib ZH, Aneke JS, Tondella ML, Zaki Q, Cassiday PK, Lonsway D, Farrque M, Hossen T, Feldstein LR, Cook N, Maldonado-Quiles G, Alam AN, Muraduzzaman AK, Akram A, Conklin L, Doan S, Friedman M, Acosta AM, Hariri S, Fox LM, Tiwari TS, Flora MS.
        J Infect Dis. 2020 Nov 27.
        BACKGROUND: Diphtheria, a life-threatening respiratory disease, is caused mainly by toxin-producing strains of Corynebacterium diphtheriae, while nontoxigenic Corynebacteria, such as C. pseudodiphtheriticum rarely causes diphtheria-like illness. Recently several global diphtheria outbreaks have resulted from the breakdown of healthcare infrastructures particularly in countries experiencing political conflict. This report summarizes a laboratory and epidemiological investigation of a diphtheria outbreak among Forcibly Displaced Myanmar Nationals in Bangladesh. METHODS: Specimens and clinical information were collected from patients presenting at Diphtheria Treatment Centers. Swabs were tested for toxin-gene (tox) bearing C. diphtheriae by real-time (RT) PCR and culture. The isolation of another Corynebacterium species prompted further laboratory investigation. RESULTS: Among 382 patients; 153 (40%) tested tox-positive for C. diphtheriae by RT-PCR; 31 (20%) PCR-positive swabs were culture-confirmed. RT-PCR revealed 78% (298/382) of patients tested positive for C. pseudodiphtheriticum. Of patients positive for only C. diphtheriae, 63% (17/27) had severe disease compared to 55% (69/126) positive for both Corynebacterium species, and 38% (66/172) for only C. pseudodiphtheriticum. CONCLUSIONS: We report the confirmation of a diphtheria outbreak and identification of a co-circulating Corynebacterium species. The high proportion of C. pseudodiphtheriticum co-detection may explain why many suspected patients testing negative for C. diphtheriae presented with diphtheria-like symptoms.

      46. A cluster-based, spatial-sampling method for assessing household healthcare utilization patterns in resource-limited settingsexternal icon
        Yu AT, Shakya R, Adhikari B, Tamrakar D, Vaidya K, Maples S, Date K, Bogoch , Bern C, Qamar F, Yousafzai MT, Garrett DO, Longley AT, Hemlock C, Luby S, Aiemjoy K, Andrews JR.
        Clin Infect Dis. 2020 Dec 1;71(Supplement_3):S239-s247.
        BACKGROUND: Implementation of population-based surveys is resource intensive and logistically demanding, especially in areas with rapidly changing demographics and incomplete or no enumeration of the underlying population and their residences. To remove the need for pre-enumeration and to simplify field logistics for the population healthcare utilization survey used for the Surveillance for Enteric Fever in Asia Project in Nepal, we incorporated a geographic information system-based geosurvey and field mapping system into a single-stage cluster sampling approach. METHODS: A survey was administered to ascertain healthcare-seeking behavior in individuals with recent suspected enteric fever. Catchment areas were based on residential addresses of enteric fever patients using study facilities; clusters were randomly selected from digitally created grids using available satellite images and all households within clusters were offered enrollment. A tablet-compatible geosurvey and mapping system that allowed for data-syncing and use in areas without cellular data was created using the ArcGIS suite of software. RESULTS: Between January 2017 and November 2018, we surveyed 25 521 households in Nepal (16 769 in urban Kathmandu and 8752 in periurban Kavrepalanchok), representing 84 202 individuals. Overall, the survey participation rate was 90.9%, with geographic heterogeneity in participation rates within each catchment area. Areas with higher average household wealth had lower participation rates. CONCLUSION: A geographic information system-based geosurvey and field mapping system allowed creation of a virtual household map at the same time as survey administration, enabling a single-stage cluster sampling method to assess healthcare utilization in Nepal for the Surveillance for Enteric Fever in Asia Project . This system removed the need for pre-enumeration of households in sampling areas, simplified logistics and could be replicated in future community surveys.

    • Disaster Control and Emergency Services
      1. Mosquito control emergency preparedness and response to natural disastersexternal icon
        Connelly CR, Borchert J.
        J Am Mosq Control Assoc. 2020 ;36(2S):2-4.

      2. Federal assistance for mosquito abatement postdisaster or during disease outbreaksexternal icon
        McAllister JC, Madson SL.
        J Am Mosq Control Assoc. 2020 ;36(2 S):74-77.
        When a disease outbreak occurs or there is increased threat for a disease outbreak to occur following a flooding disaster, it is important for government officials and mosquito abatement practitioners to know how to access federal financial, technical, or control activity assistance. In certain circumstances, the Federal Emergency Management Agency may provide reimbursement assistance to supplement state, territorial, tribal, or local governments' extraordinary mosquito abatement activities in areas that have received an emergency or major disaster declaration under the Robert T. Stafford Disaster Relief and Emergency Assistance Act (Public Law 93-288). The Centers for Disease Control and Prevention are the lead federal agency after a disease outbreak occurs. Government officials and practitioners should know how to access available assistance before an event occurs. Building a plan to request federal assistance, coordination with stakeholders under the National Incident Management System, and documentation of steps taken are the most effective method to ensure a smooth community response while maximizing assistance and reimbursement from federal agencies.

    • Disease Reservoirs and Vectors
      1. Factors modulating captures of gravid aedes aegypti femalesexternal icon
        Barrera R, Amador M, Ruiz-Valcarcel J, Acevedo V.
        J Am Mosq Control Assoc. 2020 ;36(2):66-73.
        To improve detection and assessment of Aedes aegypti abundance, we investigated whether microhabitat factors of the location of autocidal gravid ovitraps (AGO traps) influenced captures of gravid females in 2 locations in southern Puerto Rico. One location had been under vector control for several years using mass AGO trapping (intervention site), where Ae. aegypti abundance was several times lower than in the other study site without mosquito control (nonintervention site). We observed 10 environmental factors describing trap microhabitat location, and monitored water volume and minimum, maximum, and average temperature in AGO traps. Air temperature, relative humidity, and rainfall were recorded at each site. We conducted a hot-spot analysis of AGO traps to understand whether trap captures were influenced by the local abundance of mosquitoes rather than or in addition to trap microhabitat factors. AGO traps were classified using a 2-step cluster analysis based on attributes of trap microhabitats, water temperature, and water volume. Captures of female Ae. aegypti in each cluster per site were compared between resulting clusters to determine whether trap microhabitat factors defining the clusters were associated with trap captures. Trap captures in both study sites were mostly correlated with captures in nearby traps regardless of trap microhabitat factors, possibly reflecting the influence of the spatial aggregation of mosquitoes coming from nearby aquatic habitats or the concentration of dispersing adults. These results indicated that AGO traps can be located at places that can be easily reached during periodic inspections, such as in front of houses, without much regard to local microhabitat conditions.

      2. Landscape disturbance impacts on Attalea butyracea palm distribution in central Panamaexternal icon
        Mertzlufft CE, Madden M, Gottdenker NL, Velásquez Runk J, Saldaña A, Tanner S, Calzada JE, Yao X.
        Int J Health Geogr. 2020 Dec 9;19(1):58.
        BACKGROUND: Increased Attalea butyracea palm propagation, notable for its role as key habitat for the primary Chagas disease vector in Panama, has been linked to landscape disturbance in single-palm observations in this region. Close proximity of these palms to human dwellings is proposed to increase risk of Chagas disease transmission from sylvatic transmission cycles to domestic transmission involving human populations. This study examines the relationship between landscape disturbance and mature A. butyracea spatial distribution, density, and proximity to human populations and vector and reservoir species' movement corridors at a regional scale in a 300 km(2) heterogeneous tropical landscape in central Panama. METHODS: We remotely identified the locations of over 50,000 mature A. butyracea palms using high-resolution WorldView2 satellite imagery. A local Getis-Ord Gi* spatial analysis identified significant clusters of aggregated palms. Associations between palm and cluster abundance and a landscape disturbance gradient, derived from official Panama land cover data, were tested using Chi-square tests for Homogeneity and Z-test for proportions. Kruskall-Wallis non-parametric analysis of variance tests were run to assess whether palm cluster area varied by disturbance level, or whether disturbance was associated with proximity of palms and palm clusters to susceptible populations or vector movement corridors. RESULTS: Our findings indicate a regional relationship between landscape disturbance and A. butyracea occurrence. We observe a significant increase in both individual and clustered A. butyracea in secondary forest, but a reduction of palms in agricultural settings. We do not detect evidence of any reduction in abundance of palms in residential settings. The majority of residential and commercial buildings in our study area are within vector flight distance of potential vector habitat in palm crowns. CONCLUSIONS: We observe probable anthropogenic elimination of A. butyracea palms in agricultural, but not residential, settings. Even in heavily deforested regions, significant concentrations of mature palms remain in close proximity to human establishments.

      3. High MERS-CoV seropositivity associated with camel herd profile, husbandry practices and household socio-demographic characteristics in Northern Kenyaexternal icon
        Ngere I, Munyua P, Harcourt J, Hunsperger E, Thornburg N, Muturi M, Osoro E, Gachohi J, Bodha B, Okotu B, Oyugi J, Jaoko W, Mwatondo A, Njenga K, Widdowson MA.
        Epidemiol Infect. 2020 Dec 1:1-31.

      4. An update of the mosquito records of Florida counties, USAexternal icon
        Riles MT, Connelly CR.
        J Am Mosq Control Assoc. 2020 ;36(2):107-111.
        In the last 2 decades, many new Florida county mosquito records have been discovered. The intent of this report is to establish unpublished county records to update the known distribution of mosquito species in Florida. We report 92 new county records from 5 major sources collected during 1989-2019.

    • Environmental Health
      1. Exploring community psychosocial stress related to per- and poly-fluoroalkyl substances (PFAS) Contamination: Lessons learned from a qualitative studyexternal icon
        Calloway EE, Chiappone AL, Schmitt HJ, Sullivan D, Gerhardstein B, Tucker PG, Rayman J, Yaroch AL.
        Int J Environ Res Public Health. 2020 Nov 24;17(23).
        The purpose of this study was to qualitatively explore the per- and poly-fluoroalkyl substances (PFAS) exposure experience and associated stressors, to inform public health efforts to support psychosocial health and resilience in affected communities. Semi-structured interviews (n = 9) were conducted from July-September 2019 with community members and state public health department representatives from areas with PFAS-contaminated drinking water. Thematic analysis was completed and themes were described and summarized. Reported stressors included health concerns and uncertainty, institutional delegitimization and associated distrust, and financial burdens. Interviewees provided several strategies to reduce stress and promote stress coping capacity and resilience, including showing empathy and validating the normalcy of experiencing stress; building trust through visible action and sustained community engagement; providing information and actionable guidance; discussing stress carefully; fostering stress coping capacity and resilience with opportunities to build social capital and restore agency; and building capacity among government agencies and health care providers to address psychosocial stress. While communities affected by PFAS contamination will face unavoidable stressors, positive interactions with government responders and health care providers may help reduce negative stress. More research on how best to integrate community psychosocial health and stress coping and resilience concepts into the public health response to environmental contamination could be helpful in addressing these stressors.

      2. Uncontrolled asthma and household environmental exposures in Puerto Ricoexternal icon
        Cowan KN, Qin X, Ruiz Serrano K, Sircar K, Pennington AF.
        J Asthma. 2020 Dec 3:1-10.
        OBJECTIVE: To describe asthma control and household environmental exposures among adults and children with asthma in Puerto Rico. METHODS: A cross-sectional analysis was conducted using data from the 2014-2016 Behavioral Risk Factor Surveillance System Asthma Call-back Survey on 931 adults and 177 children with current asthma in Puerto Rico. These data were analyzed to assess the prevalence of uncontrolled asthma in Puerto Rico and potential associations with household environmental exposure to cockroaches, smoke, and mold. Asthma control was classified using daytime and nighttime symptoms, activity limitation, and short-acting beta agonist use. Prevalence and prevalence ratios were calculated, adjusting for sample weighting. RESULTS: An estimated 53% of adults with asthma and 29% of children with asthma in Puerto Rico have uncontrolled asthma. Among adults with asthma, in the past 30 days, 29% had seen or smelled mold and 50% had seen cockroaches; in the past week, 12% reported having someone smoke in their home. Adults with uncontrolled asthma were 1.4 times more likely to have observed mold in their homes than were those with controlled asthma when adjusting for age, sex, education, and income (prevalence ratio [95% confidence interval]: 1.4 [1.1, 1.8]). Children with uncontrolled asthma were also more likely to have mold observed in their home than were children with controlled asthma (adjusted PR[95% CI]: 3.0 [1.3, 7.1]). CONCLUSIONS: Uncontrolled asthma is common among adults and children with asthma in Puerto Rico. These results suggest potential differences in household mold exposure by asthma control status.

      3. Examination of xylene exposure in the U.S. population through biomonitoring: NHANES 2005-2006, 2011-2016external icon
        De Jesús VR, Milan DF, Yoo YM, Zhang L, Zhu W, Bhandari D, Murnane KS, Blount BC.
        Biomarkers. 2020 Dec 7:1-31.
        Xylenes are aromatic hydrocarbons used for industrial applications such as the production of petrochemicals and plastics. Acute xylene exposures can negatively impact health through neurotoxicity and irritation of respiratory and dermal tissues. We quantified urinary biomarkers of xylene exposure [2-methylhippuric acid (2MHA) and a mixture of 3- and 4-methylhippuric acids (34MH)] in a representative sample of the U.S. population. Spot urine obtained during the National Health and Nutrition Examination Survey 2005-2006 and 2011-2016 was analyzed using ultra-high-performance liquid chromatography/tandem mass spectrometry. Exclusive smokers were distinguished from non-users using a combination of self-report and serum cotinine data. The median 2MHA and 34MH levels were higher for exclusive smokers (100 µg/g and 748 µg/g creatinine, respectively) than for non-users (27.4 µg/g and 168 µg/g creatinine, respectively). Participants who smoked cigarettes had significantly higher 2MHA and 34MH levels (p < 0.0001) than unexposed participants. Smoking 1-10, 11-20, and >20 cigarettes per day (CPD) was significantly associated with 181%, 339% and 393% higher 2MHA levels, respectively. For 34MH, smoking 1-10, 11-20, and >20 CPD was significantly associated with 201%, 398%, and 471% higher 34MH levels, respectively. We confirm that tobacco smoke is a significant source of xylene exposure as measured by urinary 2MHA and 34MH levels.

      4. Exposure to per- and polyfluoroalkyl substances and adiposity at age 12 years: Evaluating periods of susceptibilityexternal icon
        Liu Y, Li N, Papandonatos GD, Calafat AM, Eaton CB, Kelsey KT, Chen A, Lanphear BP, Cecil KM, Kalkwarf HJ, Yolton K, Braun JM.
        Environ Sci Technol. 2020 Dec 3.
        Per- and polyfluoroalkyl substances (PFAS) exposure may increase adiposity and obesity risk in children. However, no studies have extended these findings into adolescence or identified periods of heightened susceptibility. We estimated associations of repeated pre- and postnatal serum PFAS concentrations with adolescent adiposity and risk of overweight/obesity. We studied 212 mother-offspring pairs from the HOME Study. We quantified serum concentrations of four PFAS in mothers at ∼16 week gestation and their children at birth and ages 3, 8, and 12 years. We assessed adiposity at 12 years using anthropometry and dual-energy X-ray absorptiometry. Using multiple informant models, we estimated covariate-adjusted associations of an interquartile range (IQR) increase in log(2)-transformed PFAS for each time period with adiposity measures and tested differences in these associations. Serum perfluorooctanoate (PFOA) and perfluorohexane sulfonate (PFHxS) concentrations during pregnancy were associated with modest increases in central adiposity and risk of overweight/obesity, but there was no consistent pattern for postnatal concentrations. We observed nonlinear associations between PFOA in pregnancy and some measures of adiposity. Overall, we observed a pattern of modest positive associations of gestational PFOA and PFHxS concentrations with central adiposity and the risk of obesity in adolescents, while no pattern was observed for postnatal PFAS concentrations.

      5. How indigenous communities are adapting to climate change: Insights from the Climate-Ready Tribes Initiativeexternal icon
        Schramm PJ, Al Janabi AL, Campbell LW, Donatuto JL, Gaughen SC.
        Health Aff (Millwood). 2020 Dec;39(12):2153-2159.
        Climate change directly threatens human health, with substantial impacts on Indigenous peoples, who are uniquely vulnerable as climate-related events affect their practices, lifeways, self-determination, and physical and cultural health. At the same time, Indigenous communities are leading the way in innovative health-related climate change adaptation work, using traditional knowledges and novel approaches. In 2016 the Centers for Disease Control and Prevention and the National Indian Health Board created the Climate-Ready Tribes Initiative to support these efforts. The initiative has funded tribes, shared information nationally, and supported a learning cohort, resulting in pioneering work to protect health from climate hazards. We describe how two tribes-the Pala Band of Mission Indians and the Swinomish Indian Tribal Community-implemented their Climate-Ready Tribes Initiative projects, and we provide recommendations for making climate and health policy more effective for tribes. Lessons learned from the Climate-Ready Tribes Initiative can inform climate and health policy and practice nationwide.

    • Epidemiology and Surveillance
      1. Population size estimation methods: Searching for the holy grailexternal icon
        Neal JJ, Prybylski D, Sanchez T, Hladik W.
        JMIR Public Health Surveill. 2020 Dec 3;6(4):e25076.
        Accurate size estimates of key populations (eg, sex workers, people who inject drugs, transgender people, and men who have sex with men) can help to ensure adequate availability of services to prevent or treat HIV infection; inform HIV response planning, target setting, and resource allocation; and provide data for monitoring and evaluating program outcomes and impact. A gold standard method for population size estimation does not exist, but quality of estimates could be improved by using empirical methods, multiple data sources, and sound statistical concepts. To highlight such methods, a special collection of papers in JMIR Public Health and Surveillance has been released under the title "Key Population Size Estimations." We provide a summary of these papers to highlight advances in the use of empirical methods and call attention to persistent gaps in information.

    • Genetics and Genomics
      1. Genomic epidemiology of nontoxigenic Corynebacterium diphtheriae from King County, Washington State, USA between July 2018 and May 2019external icon
        Xiaoli L, Benoliel E, Peng Y, Aneke J, Cassiday PK, Kay M, McKeirnan S, Duchin JS, Kawakami V, Lindquist S, Acosta AM, DeBolt C, Tondella ML, Weigand MR.
        Microb Genom. 2020 Dec 4.
        Between July 2018 and May 2019, Corynebacterium diphtheriae was isolated from eight patients with non-respiratory infections, seven of whom experienced homelessness and had stayed at shelters in King County, WA, USA. All isolates were microbiologically identified as nontoxigenic C. diphtheriae biovar mitis. Whole-genome sequencing confirmed that all case isolates were genetically related, associated with sequence type 445 and differing by fewer than 24 single-nucleotide polymorphisms (SNPs). Compared to publicly available C. diphtheriae genomic data, these WA isolates formed a discrete cluster with SNP variation consistent with previously reported outbreaks. Virulence-related gene content variation within the highly related WA cluster isolates was also observed. These results indicated that genome characterization can readily support epidemiology of nontoxigenic C. diphtheriae.

    • Health Disparities
      1. Impact of the United States federal child tax credit on childhood injuries and behavior problemsexternal icon
        Rostad WL, Klevens J, Ports KA, Ford DC.
        Child Youth Serv Rev. 2019 Feb;107.
        Children who grow up in poverty are at risk for various poor outcomes. Socioeconomic policies can shape the conditions in which families are raising children and may be effective at reducing financial strain and helping families obtain economic sufficiency, thereby reducing risk for poor health outcomes. This study used data from two surveys conducted in the US, the National Longitudinal Survey of Youth 1979 (NLSY79) and the NLSY79 Young Adult survey to determine whether the U.S. Federal Child Tax Credit (CTC), a socioeconomic policy that provides tax relief to low- and middle-income families to offset the costs of raising children, is associated with child well-being, as indicated by whether the child had injuries requiring medical attention and behavioral problems. Fixed-effects models, accounting for year and state of residence, detected a lower likelihood of injuries requiring medical attention (OR = 0.58, 95% CI [0.40, 0.86]) and significantly fewer behavior problems (b = -2.07, 95% CI [-4.06, -0.08]) among children with mothers eligible to receive a CTC, but only when it was partially refundable (i.e., mothers could receive a tax refund for a portion of the CTC that exceeds their tax liability) for families making as little as $3000 a year. Tax credits like the CTC have the potential to alleviate financial strain among families, and consequently, may have impacts on injury and behavior problems.

    • Health Economics
      1. A cost-effectiveness analysis of South Africa's seasonal influenza vaccination programmeexternal icon
        Edoka I, Kohli-Lynch C, Fraser H, Hofman K, Tempia S, McMorrow M, Ramkrishna W, Lambach P, Hutubessy R, Cohen C.
        Vaccine. 2020 Nov 30.
        BACKGROUND: Seasonal influenza imposes a significant health and economic burden in South Africa, particularly in populations vulnerable to severe consequences of influenza. This study assesses the cost-effectiveness of South Africa's seasonal influenza vaccination strategy, which involves vaccinating vulnerable populations with trivalent inactivated influenza vaccine (TIV) during routine facility visits. Vulnerable populations included in our analysis are persons aged ≥ 65 years; pregnant women; persons living with HIV/AIDS (PLWHA), persons of any age with underlying medical conditions (UMC) and children aged 6-59 months. METHOD: We employed the World Health Organisation's (WHO) Cost Effectiveness Tool for Seasonal Influenza Vaccination (CETSIV), a decision tree model, to evaluate the 2018 seasonal influenza vaccination campaign from a public healthcare provider and societal perspective. CETSIV was populated with existing country-specific demographic, epidemiologic and coverage data to estimate incremental cost-effectiveness ratios (ICERs) by comparing costs and benefits of the influenza vaccination programme to no vaccination. RESULTS: The highest number of clinical events (influenza cases, outpatient visits, hospitalisation and deaths) were averted in PLWHA and persons with other UMCs. Using a cost-effectiveness threshold of US$ 3400 per quality-adjusted life year (QALY), our findings suggest that the vaccination programme is cost-effective for all vulnerable populations except for children aged 6-59 months. ICERs ranged from ~US$ 1 750 /QALY in PLWHA to ~US$ 7500/QALY in children. In probabilistic sensitivity analyses, the vaccination programme was cost-effective in pregnant women, PLWHA, persons with UMCs and persons aged ≥65 years in >80% of simulations. These findings were robust to changes in many model inputs but were most sensitive to uncertainty in estimates of influenza-associated illness burden. CONCLUSION: South Africa's seasonal influenza vaccination strategy of opportunistically targeting vulnerable populations during routine visits is cost-effective. A budget impact analysis will be useful for supporting future expansions of the programme.

      2. Generalizing about the cost-effectiveness of newborn screening (NBS) is difficult due to the heterogeneity of disorders included in NBS panels, along with data limitations. Furthermore, it is unclear to what extent evidence about cost-effectiveness should influence decisions to screen for specific disorders. Screening newborns for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can serve as a useful test case, since there is no global consensus on whether CAH should be part of NBS panels. Published and unpublished cost-effectiveness analyses of CAH screening have yielded mixed findings, largely due to differences in methods and data sources for estimating health outcomes and associated costs of early versus late diagnosis as well as between-country differences. Understanding these methodological challenges can help inform future analyses and could also help interested policymakers interpret the results of economic evaluations.

      3. The purpose of this study was to examine both the distribution of payers for inpatient hospitalizations (all-ages) by principal diagnosis status (epilepsy versus nonepilepsy) and selected organizational- and community-level factors associated with hospitalizations using the Agency for Healthcare Research and Quality's (AHRQ) Healthcare Utilization Project 2016 National Inpatient Sample (NIS) database. We compared cases with epilepsy (any ICD-10CM diagnostic code beginning with "G40") as a principal diagnosis ("epilepsy discharges") versus cases without epilepsy as the principal diagnosis ("nonepilepsy discharges"). Accounting for the complex survey design, we examined how the principal payer source, median income for Zip Code, admission type, hospital location, teaching status, and hospital region varied by principal diagnosis status. For persons of all ages with epilepsy as a principal diagnosis, Medicaid and Medicare public insurance paid for about 65% of inpatient hospitalization costs. The percentage paid by Medicaid among epilepsy discharges (31.6%) significantly exceeded that among nonepilepsy discharges (23.1%). The percentage paid by Medicare among epilepsy discharges (33.9%) was significantly less than that among nonepilepsy discharges (39.7%), as was payment by private insurers (26.1% vs. 30.1%). Median Zip Code income, hospital and admission characteristics, and geographic region differed between hospitalizations with epilepsy versus those with a nonepilepsy discharge. These findings may be used to inform stakeholders' understanding of epilepsy care-related costs and factors associated with hospitalizations for improved interventions and programs.

      4. Rural-urban differences in delivery hospitalization costs by severe maternal morbidity statusexternal icon
        Lin CC, Hirai AH, Li R, Kuklina EV, Fisher SK.
        Ann Intern Med. 2020 Dec 1;173(11_Supplement):S59-s62.

      5. Health and economic outcomes of newborn screening for infantile-onset Pompe diseaseexternal icon
        Richardson JS, Kemper AR, Grosse SD, Lam WK, Rose AM, Ahmad A, Gebremariam A, Prosser LA.
        Genet Med. 2020 Dec 7.
        PURPOSE: To estimate health and economic outcomes associated with newborn screening (NBS) for infantile-onset Pompe disease in the United States. METHODS: A decision analytic microsimulation model simulated health and economic outcomes of a birth cohort of 4 million children in the United States. Universal NBS and treatment was compared with clinical identification and treatment of infantile-onset Pompe disease. Main outcomes were projected cases identified, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) over the life course. RESULTS: Universal NBS for Pompe disease and confirmatory testing was estimated to cost an additional $26 million annually. Additional medication costs associated with earlier treatment initiation were $181 million; however, $8 million in medical care costs for other services were averted due to delayed disease progression. Infants with screened and treated infantile-onset Pompe disease experienced an average lifetime increase of 11.66 QALYs compared with clinical detection. The ICER was $379,000/QALY from a societal perspective and $408,000/QALY from the health-care perspective. Results were sensitive to the cost of enzyme replacement therapy. CONCLUSION: Newborn screening for Pompe disease results in substantial health gains for individuals with infantile-onset Pompe disease, but with additional costs.

      6. BACKGROUND: Malaria-endemic countries distribute long-lasting insecticidal nets (LLINs) through combined channels with ambitious, universal coverage (UC) targets. Kenya has used eight channels with variable results. To inform national decision-makers, this two-arm study compares coverage (effects), costs, cost-effectiveness, and equity of two combinations of LLIN distribution channels in Kenya. METHODS: Two combinations of five delivery channels were compared as 'intervention' and 'control' arms. The intervention arm comprised four channels: community health volunteer (CHV), antenatal and child health clinics (ANCC), social marketing (SM) and commercial outlets (CO). The control arm consisted of the intervention arm channels except mass campaign (MC) replaced CHV. Primary analysis used random sample household survey data, service-provider costs, and voucher or LLIN distribution data to compare between-arm effects, costs, cost-effectiveness, and equity. Secondary analyses compared costs and equity by channel. RESULTS: The multiple distribution channels used in both arms of the study achieved high LLIN ownership and use. The intervention arm had significantly lower reported LLIN use the night before the survey (84·8% [95% CI 83·0-86·4%] versus 89·2% [95% CI 87·8-90·5%], p < 0·0001), higher unit costs ($10·56 versus $7·17), was less cost-effective ($86·44, 95% range $75·77-$102·77 versus $69·20, 95% range $63·66-$77·23) and more inequitable (Concentration index [C.Ind] = 0·076 [95% CI 0·057 to 0·095 versus C.Ind = 0.049 [95% CI 0·030 to 0·067]) than the control arm. Unit cost per LLIN distributed was lowest for MC ($3·10) followed by CHV ($10·81) with both channels being moderately inequitable in favour of least-poor households. CONCLUSION: In line with best practices, the multiple distribution channel model achieved high LLIN ownership and use in this Kenyan study setting. The control-arm combination, which included MC, was the most cost-effective way to increase UC at household level. Mass campaigns, combined with continuous distribution channels, are an effective and cost-effective way to achieve UC in Kenya. The findings are relevant to other countries and donors seeking to optimise LLIN distribution. TRIAL REGISTRATION: The assignment of the intervention was not at the discretion of the investigators; therefore, this study did not require registration.

    • Healthcare Associated Infections
      1. Impact of implementation of the core elements of outpatient antibiotic stewardship within Veterans Health Administration Emergency Department and Primary Care Clinics on antibiotic prescribing and patient outcomesexternal icon
        Madaras-Kelly K, Hostler C, Townsend M, Potter EM, Spivak ES, Hall SK, Goetz MB, Nevers M, Ying J, Haaland B, Rovelsky SA, Pontefract B, Fleming-Dutra K, Hicks LA, Samore MH.
        Clin Infect Dis. 2020 Dec 8.
        BACKGROUND: The Core Elements of Outpatient Antibiotic Stewardship provide a framework to improve antibiotic use, but evidence supporting safety are limited. We report the impact of Core Elements implementation within Veterans Health Administration sites. METHODS: A quasi-experimental controlled study assessed the effects of an intervention targeting antibiotic prescription for uncomplicated acute respiratory tract infections (ARI). Outcomes included per-visit antibiotic prescribing, treatment appropriateness, potential benefits and complications of reduced antibiotic treatment, and change in ARI diagnoses over a 3-year pre-implementation and 1-year post implementation period. Logistic regression adjusted for covariates [OR (95% CI)] and a difference-in-differences analysis compared outcomes between intervention and control sites. RESULTS: From 2014-2019, there were 16,712 and 51,275 patient-visits in 10 intervention and 40 control sites, respectively. Antibiotic prescribing rates pre-post implementation in intervention sites were 59.7% and 41.5%, respectively; in control sites they were 73.5% and 67.2%, respectively [difference-in-differences p<0.001]. The intervention site pre-post implementation odds ratio to receive appropriate therapy increased [1.67 (1.31, 2.14)] which remained unchanged within control sites [1.04 (0.91, 1.19)]. There was no difference in ARI-related return visits post-implementation [(-1.3% vs. -2.0%; difference-in-differences p=0.76] but all-cause hospitalization was lower within intervention sites [(-0.5% vs. -0.2%); difference-in-differences p=0.02]. The odds ratio to diagnose upper respiratory tract infection not otherwise specified compared to other non-ARI diagnosis increased post-implementation for intervention [1.27(1.21,1.34)] but not control [0.97(0.94,1.01)] sites. CONCLUSIONS: Implementation of the Core Elements was associated with reduced antibiotic prescribing for uncomplicated ARIs and a reduction in hospitalizations. ARI diagnostic coding changes were observed.

      2. Dedicated time for antimicrobial stewardship-How much and why? Lessons learned from South Koreaexternal icon
        Patel PK, Srinivasan A.
        Infect Control Hosp Epidemiol. 2020 Dec;41(12):1436-1437.
        Antimicrobial resistance is a global and pressing problem that requires large-scale, federal coordination of efforts and tailored local interventions and surveillance. Given the urgency of the threat, many countries now have national policies to reduce inappropriate antimicrobial use. However, few countries have followed this with resources at the institutional level to support the implementation of practices to achieve this goal. In the United States, accreditation bodies such as Centers for Medicare and Medicaid Services and The Joint Commission have added antimicrobial stewardship standards to encourage uptake of antimicrobial stewardship programs (ASPs).

      3. Cryptococcus transmission through solid organ transplantation in the United States: A Report from the Ad Hoc Disease Transmission Advisory Committeeexternal icon
        Penumarthi LR, La Hoz RM, Wolfe CR, Jackson BR, Mehta AK, Malinis M, Danziger-Isakov L, Strasfeld L, Florescu DF, Vece G, Basavaraju SV, Michaels MG.
        Am J Transplant. 2020 Dec 8.
        Cryptococcus species can cause serious life-threatening infection in solid organ transplant recipients by reactivation of prior infection, post-transplant de novo infection, or donor transmission from the transplanted organ. Although previously reported in the literature, the extent of donor-derived cryptococcosis in the United States has not been documented. We analyzed potential donor-derived Cryptococcus transmission events reported to the Organ Procurement and Transplantation Network (OPTN) for investigation by the ad hoc Disease Transmission Advisory Committee (DTAC). All reports between 2009-2019 in which transmission to recipients was designated proven or probable, or determined to be averted due to implementation of prophylaxis (intervention without disease transmission - "IWDT") were included. During 2009-2019, 58 reports of potential donor-derived cryptococcosis were submitted to DTAC. Among these reports, 12 donors were determined to have resulted in proven or probable transmission to 23/34 (67.6%) recipients. Most of these donors (10/12 (83%)) exhibited central nervous system-related symptoms prior to death and 5/23 (22%) infected recipients died. For 11 different donors, prophylaxis, most often with fluconazole, was administered to 23/35 (65.7%) recipients. Clinicians should maintain awareness of donor-derived cryptococcosis and consider prompt prophylaxis or treatment followed by reporting to OPTN for further investigation.

      4. Carbapenem-resistant Acinetobacter baumannii (CRAB), an opportunistic pathogen primarily associated with hospital-acquired infections, is an urgent public health threat (1). In health care facilities, CRAB readily contaminates the patient care environment and health care providers' hands, survives for extended periods on dry surfaces, and can be spread by asymptomatically colonized persons; these factors make CRAB outbreaks in acute care hospitals difficult to control (2,3). On May 28, 2020, a New Jersey hospital (hospital A) reported a cluster of CRAB infections during a surge in patients hospitalized with coronavirus disease 2019 (COVID-19). Hospital A and the New Jersey Department of Health (NJDOH) conducted an investigation, and identified 34 patients with hospital-acquired multidrug-resistant CRAB infection or colonization during February-July 2020, including 21 (62%) who were admitted to two intensive care units (ICUs) dedicated to caring for COVID-19 patients. In late March, increasing COVID-19-related hospitalizations led to shortages in personnel, personal protective equipment (PPE), and medical equipment, resulting in changes to conventional infection prevention and control (IPC) practices. In late May, hospital A resumed normal operations, including standard IPC measures, as COVID-19 hospitalizations decreased, lessening the impact of personnel and supply chain shortages on hospital functions. CRAB cases subsequently returned to a pre-COVID-19 baseline of none to two cases monthly. The occurrence of this cluster underscores the potential for multidrug-resistant organisms (MDROs) to spread during events when standard hospital practices might be disrupted; conventional IPC strategies should be reinstated as soon as capacity and resources allow.

      5. Notes from the field: First case in the United States of Neisseria gonorrhoeae harboring emerging mosaic penA60 allele, conferring reduced susceptibility to cefixime and ceftriaxoneexternal icon
        Picker MA, Knoblock RJ, Hansen H, Bautista I, Griego R, Barber L, Bendik W, Lam K, Adelman E, Qiu-Shultz Z, Raphael BH, Pham CD, Kersh EN, Weinstock H, St Cyr SB.
        MMWR Morb Mortal Wkly Rep. 2020 Dec 11;69(49):1876-1877.

    • Immunity and Immunization
      1. Prediction of putative epitope-based vaccine against all corona virus strains for Chinese population: Approach toward development of vaccineexternal icon
        Batool H, Batool S, Mahmood MS, Mushtaq N, Khan AU, Ali M, Sahibzada KI, Ashraf NM.
        Microbiol Immunol. 2020 Dec 9.
        Currently, the whole world is facing a COVID-19 pandemic. As of now, approximately 0.15 million people around the globe are infected with the novel coronavirus. In the last decade, two strains of the coronavirus family, SARS-CoV, MERS-CoV also resulted in epidemics in south Asian and the Middle Eastern countries with high mortality rate. This scenario demands the development of a putative vaccine which may provide immunity against all current and new evolving coronavirus strains. In this study, we design an epitope-based vaccine using an immunoinformatic approach. This vaccine may protect against all coronavirus strains. The vaccine is developed by considering the geographical distribution of coronavirus strains and host genetics (Chinese population). Nine experimentally validated epitopes sequences from coronavirus strains were used to derive the variants considering the conservancy in all strains. Further, the binding affinities of all derived variants were checked with most abundant HLA alleles in the Chinese population. Three MHC class-I epitopes from Spike glycoprotein and Nucleoprotein showed sufficient binding while one MHC class-II epitope from Spike glycoprotein found to be an effective binder. A cocktail of these epitopes gave more than 95% population coverage in the Chinese population. Moreover, MD simulation also supported the above-mentioned predictions. Further, in vivo studies are needed to confirm the immunogenic potential of these vaccines. This article is protected by copyright. All rights reserved.

      2. The Advisory Committee on Immunization Practices' interim recommendation for allocating initial supplies of COVID-19 vaccine - United States, 2020external icon
        Dooling K, McClung N, Chamberland M, Marin M, Wallace M, Bell BP, Lee GM, Talbot HK, Romero JR, Oliver SE.
        MMWR Morb Mortal Wkly Rep. 2020 Dec 11;69(49):1857-1859.
        The emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), has led to a global pandemic that has disrupted all sectors of society. Less than 1 year after the SARS-CoV-2 genome was first sequenced, an application* for Emergency Use Authorization for a candidate vaccine has been filed with the Food and Drug Administration (FDA). However, even if one or more vaccine candidates receive authorization for emergency use, demand for COVID-19 vaccine is expected to exceed supply during the first months of the national vaccination program. The Advisory Committee on Immunization Practices (ACIP) advises CDC on population groups and circumstances for vaccine use.(†) ACIP convened on December 1, 2020, in advance of the completion of FDA's review of the Emergency Use Authorization application, to provide interim guidance to federal, state, and local jurisdictions on allocation of initial doses of COVID-19 vaccine. ACIP recommended that, when a COVID-19 vaccine is authorized by FDA and recommended by ACIP, both 1) health care personnel(§) and 2) residents of long-term care facilities (LTCFs)(¶) be offered vaccination in the initial phase of the COVID-19 vaccination program (Phase 1a**).(††) In its deliberations, ACIP considered scientific evidence of SARS-CoV-2 epidemiology, vaccination program implementation, and ethical principles.(§§) The interim recommendation might be updated over the coming weeks based on additional safety and efficacy data from phase III clinical trials and conditions of FDA Emergency Use Authorization.

      3. INTRODUCTION: In 2006 and 2008, two live, oral rotavirus vaccines, RotaTeq (RV5) and Rotarix (RV1), were introduced into the routine immunization program in the United States. A previous rotavirus vaccine, RotaShield, was associated with an increased risk of intussusception, with data suggesting an age-dependent variation in risk. Advisory Committee on Immunization Practices (ACIP) currently recommends that RV5 or RV1 immunization be initiated by age 14 weeks and 6 days and completed by 8 months 0 days. METHODS: We searched for U.S. VAERS reports of RV5, RV1, or unknown rotavirus vaccine brand among individuals aged ≥8 months. We analyzed reports by 2 age groups (individuals aged ≥8 months-≤5 years and ≥6 years), vaccine brand name, adverse event (AE) reported, classification of seriousness (death, non-death serious, and non-serious) and mode of exposure (direct vs. indirect exposure). For serious reports we reviewed available medical records and assigned a primary diagnosis. RESULTS: VAERS received a total of 344 U.S. reports following rotavirus vaccination among individuals ≥8 months of age, 32 (9.3%) were serious. In the younger age-group, 307 (99%) of 309 reports followed direct vaccination of the child. In contrast, in individuals aged ≥6 years, 21 (60%) of 35 reports were via potential indirect exposure to a vaccinated child. The frequently reported AEs in the younger age-group were inappropriate schedule of drug administration 104 (34%) and drug administered to patient of inappropriate age 45 (15%); in the older group these were accidental exposure 9 (26%) and eye irritation 7 (20%). No difference in the safety profile was observed between RV1 and RV5. CONCLUSIONS: We did not identify any unexpected AEs for RV vaccines among individuals aged ≥8 months. Health care providers should adhere to the ACIP recommended schedule and older individuals should apply necessary precautions to prevent potential secondary exposure from vaccinated children.

      4. Comparison of influenza antibody titers among women who were vaccinated in the 2(nd) and the 3(rd) trimesters of pregnancyexternal icon
        Kittikraisak W, Phadungkiatwatana P, Ditsungnoen D, Kaoiean S, Macareo L, Rungrojcharoenkit K, Srisantiroj N, Chotpitayasunondh T, Dawood FS, Mott JA, Lindblade KA.
        Vaccine. 2020 Nov 23.
        BACKGROUND: We compared cord blood antibody titers in unvaccinated pregnant women to those vaccinated with seasonal influenza vaccine during the 2(nd) and the 3(rd) trimesters. METHODS: Pregnant women had cord blood collected at delivery for hemagglutination inhibition assay against vaccine reference viruses: A/California/07/2009 (H1N1)pdm09, A/Switzerland/9715293/2013 (H3N2), and B/Phuket/3073/2013 (Yamagata lineage). Geometric mean titer (GMT) ratios were calculated comparing vaccinated versus unvaccinated pregnant women, and women vaccinated in the 2(nd) and the 3(rd) trimesters. Proportions of women achieving defined titers were compared using the χ(2) test. RESULTS: Of 307 women, 190 (62%) were unvaccinated. Fifty and 67 were vaccinated during the 2(nd) and the 3(rd) trimesters, respectively. Median enrollment age was 29 years (interquartile range 24-34). Sixteen (5%) women had pre-existing conditions, but none were immunocompromised. GMT ratios comparing vaccinated and unvaccinated women were 5.90 (95% confidence interval [CI] 5.06-6.96) for influenza A/California, 5.39 (95% CI 4.18-6.08) for influenza A/Switzerland, and 5.05 (95% CI 4.43-5.85) for influenza B/Phuket. Similarly, the GMT ratios comparing the 3(rd) and the 2(nd) trimester vaccinated women were 2.90 (95% CI 2.54-3.39), 2.82 (95% CI 2.56-3.13), and 2.83 (95% CI 2.56-3.14), respectively. The proportions of women with defined titers for the three vaccine reference viruses did not differ between 2(nd) and 3(rd) trimester vaccinated women (titers ≥40: 68-92% versus 70-93%; ≥110: 32% versus 33-63%; and ≥330: 4-10% versus 3-21%). CONCLUSIONS: Pregnant women vaccinated against influenza had more placental transfer of influenza antibodies to their infants than unvaccinated women. Placental transfer of antibodies was higher among those vaccinated in the 3(rd) trimester than in the 2(nd) trimester. There was no difference in the proportions of women achieving antibody titers corresponding to protection against influenza in children. Findings support the current World Health Organization's recommendation that pregnant women may be vaccinated in either 2(nd) or 3(rd) trimester of pregnancy.

      5. Multiple introductions and predominance of rotavirus group A genotype G3P[8] in Kilifi, Coastal Kenya, 4 years after nationwide vaccine introductionexternal icon
        Mwanga MJ, Verani JR, Omore R, Tate JE, Parashar UD, Murunga N, Gicheru E, Breiman RF, Nokes DJ, Agoti CN.
        Pathogens. 2020 Nov 24;9(12).
        Globally, rotavirus group A (RVA) remains a major cause of severe childhood diarrhea, despite the use of vaccines in more than 100 countries. RVA sequencing for local outbreaks facilitates investigation into strain composition, origins, spread, and vaccine failure. In 2018, we collected 248 stool samples from children aged less than 13 years admitted with diarrheal illness to Kilifi County Hospital, coastal Kenya. Antigen screening detected RVA in 55 samples (22.2%). Of these, VP7 (G) and VP4 (P) segments were successfully sequenced in 48 (87.3%) and phylogenetic analysis based on the VP7 sequences identified seven genetic clusters with six different GP combinations: G3P[8], G1P[8], G2P[4], G2P[8], G9P[8] and G12P[8]. The G3P[8] strains predominated the season (n = 37, 67.2%) and comprised three distinct G3 genetic clusters that fell within Lineage I and IX (the latter also known as equine-like G3 Lineage). Both the two G3 lineages have been recently detected in several countries. Our study is the first to document African children infected with G3 Lineage IX. These data highlight the global nature of RVA transmission and the importance of increasing global rotavirus vaccine coverage.

      6. Urban-rural disparities in vaccination service use among low-income adolescentsexternal icon
        Tsai Y, Lindley MC, Zhou F, Stokley S.
        J Adolesc Health. 2020 Dec 4.
        OBJECTIVE: To access urban-rural disparities in vaccination service use among Medicaid-enrolled adolescents and examine its association with residence county characteristics. STUDY DESIGN: We used the 2016 Medicaid T-MSIS Analytic File to estimate adolescents' use of vaccination services, defined as the proportion of adolescents aged 11-18 years with ≥ 1 vaccination visit in a county. We used linear regression and the Oaxaca-Blinder decomposition method to examine the association between county characteristics and urban-rural disparities in vaccination service use. RESULTS: The analysis included 2,473 counties located in 38 states. The mean proportion of adolescents making ≥ 1 vaccination visit at the county level was low (36.09%) and was lower in rural than in urban counties (31.99% vs. 36.85%, p < .01). The number of primary care physicians (PCPs) was positively associated with vaccination service use in rural counties; in urban counties, % of households without a vehicle was negatively associated with vaccination service use. The decomposition results showed that 66.78% (3.24 percentage points) of the urban-rural disparities in vaccination service use could be attributed to urban-rural differences in the county characteristics included in the study. Characteristics measuring access to care (number of PCPs), social and economic factors (% adults with at least a bachelor's degree and % children in poverty), quality of care (influenza vaccination rates and preventable hospital stays), and demographics (% non-Hispanic black, % Hispanic, and % females) played a role in urban-rural disparities. CONCLUSIONS: Differences in county characteristics could partly explain the observed urban-rural disparities in vaccination service use among low-income adolescents.

      7. Effect of 10-valent pneumococcal conjugate vaccine on Streptococcus pneumoniae nasopharyngeal carriage among children less than 5 years old: 3 years post-10-valent pneumococcal conjugate vaccine introduction in Mozambiqueexternal icon
        Valenciano SJ, Moiane B, Lessa FC, Chaúque A, Massora S, Pimenta FC, Mucavele H, Verani JR, da Gloria Carvalho M, Whitney CG, Tembe N, Sigaúque B.
        J Pediatric Infect Dis Soc. 2020 Nov 27.
        BACKGROUND: Mozambique introduced 10-valent pneumococcal conjugate vaccine (PCV10) in 2013 with doses at ages 2, 3, and 4 months and no catch-up or booster dose. We evaluated PCV10 impact on the carriage of vaccine-type (VT), non-VT, and antimicrobial non-susceptible pneumococci 3 years after introduction. METHODS: We conducted cross-sectional carriage surveys among HIV-infected and HIV-uninfected children aged 6 weeks to 59 months: 1 pre-PCV10 (2012-2013 [Baseline]) and 2 post-PCV10 introductions (2014-2015 [Post1] and 2015-2016 [Post2]). Pneumococci isolated from nasopharyngeal swabs underwent Quellung serotyping and antimicrobial susceptibility testing. Non-susceptible isolates (intermediate or resistant) were defined using Clinical and Laboratory Standards Institute 2018 breakpoints. We used log-binomial regression to estimate changes in the pneumococcal carriage between survey periods. We compared proportions of non-susceptible pneumococci between Baseline and Post2. RESULTS: We enrolled 720 children at Baseline, 911 at Post1, and 1208 at Post2. Baseline VT carriage was similar for HIV-uninfected (36.0%, 110/306) and HIV-infected children (34.8%, 144/414). VT carriage was 36% (95% confidence interval [CI]: 19%-49%) and 27% (95% CI: 11%-41%) lower in Post1 vs baseline among HIV-uninfected and HIV-infected children, respectively. VT carriage prevalence declined in Post2 vs Post1 for HIV-uninfected but remained stable for HIV-infected children. VT carriage prevalence 3 years after PCV10 introduction was 14.5% in HIV-uninfected and 21.0% in HIV-infected children. Pneumococcal isolates non-susceptible to penicillin declined from 66.0% to 56.2% (P= .0281) among HIV-infected children. CONCLUSIONS: VT and antimicrobial non-susceptible pneumococci carriage dropped after PCV10 introduction, especially in HIV-uninfected children. However, VT carriage remained common, indicating ongoing VT pneumococci transmission.

    • Informatics
      1. Accurate spatiotemporal mapping of drug overdose deaths by machine learning of drug-related web-searchesexternal icon
        Campo DS, Gussler JW, Sue A, Skums P, Khudyakov Y.
        PLoS One. 2020 ;15(12):e0243622.
        Persons who inject drugs (PWID) are at increased risk for overdose death (ODD), infections with HIV, hepatitis B (HBV) and hepatitis C virus (HCV), and noninfectious health conditions. Spatiotemporal identification of PWID communities is essential for developing efficient and cost-effective public health interventions for reducing morbidity and mortality associated with injection-drug use (IDU). Reported ODDs are a strong indicator of the extent of IDU in different geographic regions. However, ODD quantification can take time, with delays in ODD reporting occurring due to a range of factors including death investigation and drug testing. This delayed ODD reporting may affect efficient early interventions for infectious diseases. We present a novel model, Dynamic Overdose Vulnerability Estimator (DOVE), for assessment and spatiotemporal mapping of ODDs in different U.S. jurisdictions. Using Google® Web-search volumes (i.e., the fraction of all searches that include certain words), we identified a strong association between the reported ODD rates and drug-related search terms for 2004-2017. A machine learning model (Extremely Random Forest) was developed to produce yearly ODD estimates at state and county levels, as well as monthly estimates at state level. Regarding the total number of ODDs per year, DOVE's error was only 3.52% (Median Absolute Error, MAE) in the United States for 2005-2017. DOVE estimated 66,463 ODDs out of the reported 70,237 (94.48%) during 2017. For that year, the MAE of the individual ODD rates was 4.43%, 7.34%, and 12.75% among yearly estimates for states, yearly estimates for counties, and monthly estimates for states, respectively. These results indicate suitability of the DOVE ODD estimates for dynamic IDU assessment in most states, which may alert for possible increased morbidity and mortality associated with IDU. ODD estimates produced by DOVE offer an opportunity for a spatiotemporal ODD mapping. Timely identification of potential mortality trends among PWID might assist in developing efficient ODD prevention and HBV, HCV, and HIV infection elimination programs by targeting public health interventions to the most vulnerable PWID communities.

    • Injury and Violence
      1. History of concussion is associated with substance use. Data from the 2017 National Youth Risk Behavior Survey (N = 14,765) were used in this study to examine associations between sports- or physical activity-related concussions and current cigarette, alcohol, and marijuana use among high school students, and whether other factors moderate those associations. In addition to having played on a sports team, potential moderators examined included persistent feelings of sadness or hopelessness, hours of sleep, and serious difficulty concentrating, remembering, or making decisions. The association between sports- or physical activity-related concussions and current cigarette, alcohol, and marijuana use was significant when controlling for sex, grade, and race/ethnicity and the potential moderators with the exception of cigarette smoking while controlling for hours of sleep. Those involved in the care of high school students after a concussion may consider assessing current cigarette, alcohol, and marijuana use.

      2. The purpose of this study was to assess whether the endorsement of inequitable gender norms about intimate partner violence against women (IPVAW) and sexual behavior was associated with intimate partner violence (IPV) victimization, IPV perpetration, and sexual risk behavior. Nigerian youth aged 13-24 (n = 4,203) participated in the nationally representative, cross-sectional Nigeria Violence Against Children Survey (VACS) in 2014. Inequitable gender norms about IPVAW were assessed using six items from the Demographic and Health Surveys (DHS), and inequitable gender norms about sexual behavior were assessed using four items adapted from the Gender-Equitable Men (GEM) scale. The number of inequitable gender norms endorsed was summed and associations with having been a victim or perpetrator of IPV and sexual risk behaviors were assessed using logistic regression. Endorsing 3 or more inequitable gender norms about either IPVAW or sexual behavior were both associated with increased odds of IPV victimization, perpetration, and sexual risk behaviors, after adjustment for demographic characteristics, witnessing violence in childhood, and having been a victim of other forms of childhood violence. Demonstrating that endorsement of inequitable gender norms about sexual behavior was associated with violence and that inequitable gender norms about IPVAW were associated with sexual risk behaviors further highlights potential linkages between violence and HIV.

      3. PROBLEM/CONDITION: In 2017, approximately 67,000 persons died of violence-related injuries in the United States. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) on violent deaths that occurred in 34 states, four California counties, the District of Columbia, and Puerto Rico in 2017. Results are reported by sex, age group, race/ethnicity, method of injury, type of location where the injury occurred, circumstances of injury, and other selected characteristics. PERIOD COVERED: 2017. DESCRIPTION OF SYSTEM: NVDRS collects data regarding violent deaths obtained from death certificates, coroner and medical examiner reports, and law enforcement reports. This report includes data collected for violent deaths that occurred in 2017. Data were collected from 34 states (Alaska, Arizona, Colorado, Connecticut, Delaware, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Maine, Maryland, Massachusetts, Michigan, Minnesota, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Utah, Vermont, Virginia, Washington, West Virginia, and Wisconsin), four California counties (Los Angeles, Sacramento, Shasta, and Siskiyou), the District of Columbia, and Puerto Rico. NVDRS collates information for each death and links deaths that are related (e.g., multiple homicides, homicide followed by suicide, or multiple suicides) into a single incident. RESULTS: For 2017, NVDRS collected information on 45,141 fatal incidents involving 46,389 deaths that occurred in 34 states, four California counties, and the District of Columbia; in addition, information was collected on 961 fatal incidents involving 1,027 deaths in Puerto Rico. Data for Puerto Rico were analyzed separately. Of the 46,389 deaths in the 34 states, four California counties, and District of Columbia, the majority (63.5%) were suicides, followed by homicides (24.9%), deaths of undetermined intent (9.7%), legal intervention deaths (1.4%) (i.e., deaths caused by law enforcement and other persons with legal authority to use deadly force acting in the line of duty, excluding legal executions), and unintentional firearm deaths (<1.0%). (The term "legal intervention" is a classification incorporated into the International Classification of Diseases, Tenth Revision, and does not denote the lawfulness or legality of the circumstances surrounding a death caused by law enforcement.) Demographic patterns and circumstances varied by manner of death. The suicide rate was higher among males than among females and was highest among adults aged 45-64 years and ≥85 years and non-Hispanic American Indians/Alaska Natives and non-Hispanic Whites. The most common method of injury for suicide was a firearm among males and poisoning among females. Suicide was most often preceded by a mental health, intimate partner, or physical health problem or a recent or impending crisis during the previous or upcoming 2 weeks. The homicide rate was highest among persons aged 20-24 years and was higher among males than females. Non-Hispanic Black males had the highest homicide rate of any racial/ethnic group. The most common method of injury for homicide was a firearm. When the relationship between a homicide victim and a suspect was known, the suspect was most frequently an acquaintance or friend for male victims and a current or former intimate partner for female victims. Homicide most often was precipitated by an argument or conflict, occurred in conjunction with another crime, or, for female victims, was related to intimate partner violence. Among intimate partner violence-related homicides, the largest proportion occurred among adults aged 35-54 years, and the most common method of injury was a firearm. When the relationship between an intimate partner violence-related homicide victim and a suspect was known, most female victims were killed by a current or former intimate partner, whereas approximately half of male victims were killed by a suspect who was not their intimate partner. Almost all legal intervention deaths were among males, and the legal intervention death rate was highest among men aged 25-29 years. Non-Hispanic American Indian/Alaska Native males had the highest legal intervention death rate, followed by non-Hispanic Black males. A firearm was used in the majority of legal intervention deaths. When a specific type of crime was known to have precipitated a legal intervention death, the type of crime was most frequently assault/homicide. The most frequent circumstances for legal intervention deaths were reported use of a weapon by the victim in the incident and a mental health or substance use problem (other than alcohol use). Unintentional firearm deaths more frequently occurred among males, non-Hispanic Whites, and persons aged 15-24 years. These deaths most often occurred while the shooter was playing with a firearm and most frequently were precipitated by a person unintentionally pulling the trigger or mistakenly thinking the firearm was unloaded. The rate of death when the manner was of undetermined intent was highest among males, particularly among non-Hispanic Black and non-Hispanic American Indian/Alaska Native males, and persons aged 30-34 years. Poisoning was the most common method of injury in deaths of undetermined intent, and opioids were detected in nearly 80% of decedents tested for those substances. INTERPRETATION: This report provides a detailed summary of data from NVDRS on violent deaths that occurred in 2017. The suicide rate was highest among non-Hispanic American Indian/Alaska Native and non-Hispanic White males, whereas the homicide rate was highest among non-Hispanic Black males. Intimate partner violence precipitated a large proportion of homicides for females. Mental health problems, intimate partner problems, interpersonal conflicts, and acute life stressors were primary circumstances for multiple types of violent death. PUBLIC HEALTH ACTION: NVDRS data are used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in developing, implementing, and evaluating programs and policies to reduce and prevent violent deaths. For example, South Carolina VDRS and Colorado VDRS are using their data to support suicide prevention programs through systems change and the Zero Suicide framework. North Carolina VDRS and Kentucky VDRS data were used to examine intimate partner violence-related deaths beyond homicides to inform prevention efforts. Findings from these studies suggest that intimate partner violence might also contribute to other manners of violent death, such as suicide, and preventing intimate partner violence might reduce the overall number of violent deaths. In 2019, NVDRS expanded data collection to include all 50 states, the District of Columbia, and Puerto Rico, providing more comprehensive and actionable violent death information for public health efforts to reduce violent deaths.

      4. Heightened stress, school closures, loss of income, and social isolation resulting from the coronavirus disease 2019 (COVID-19) pandemic have increased the risk for child abuse and neglect (1). Using National Syndromic Surveillance Program (NSSP) data from January 6, 2019-September 6, 2020, CDC tabulated weekly numbers of emergency department (ED) visits related to child abuse and neglect and calculated the proportions of such visits per 100,000 ED visits, as well as the percentage of suspected or confirmed ED visits related to child abuse and neglect ending in hospitalization, overall and stratified by age group (0-4, 5-11, and 12-17 years). The total number of ED visits related to child abuse and neglect began decreasing below the corresponding 2019 period during week 11 (March 15-March 22, 2020) for all age groups examined, coinciding with the declaration of a national emergency on March 13 (2); simultaneously, the proportion of these visits per 100,000 ED visits began increasing above the 2019 baseline for all age groups. Despite decreases in the weekly number of ED visits related to child abuse and neglect, the weekly number of these visits resulting in hospitalization remained stable in 2020; however, the yearly percentage of ED visits related to child abuse and neglect resulting in hospitalization increased significantly among all age groups. Although the increased proportion of ED visits related to child abuse and neglect might be associated with a decrease in the overall number of ED visits, these findings also suggest that health care-seeking patterns have shifted during the pandemic. Hospitalizations for child abuse and neglect did not decrease in 2020, suggesting that injury severity did not decrease during the pandemic, despite decreased ED visits. Child abuse is preventable; implementation of strategies including strengthening household economic supports and creating family-friendly work policies can reduce stress during difficult times and increase children's opportunities to thrive in safe, stable, and nurturing relationships and environments (3).

    • Laboratory Sciences
      1. Development of diagnostic microsphere-based immunoassays for Heartland virusexternal icon
        Basile AJ, Horiuchi K, Goodman CH, Kosoy O, Panella AJ, Velez JO, Pastula DM, Brault AC, Staples JE, Calvert AE.
        J Clin Virol. 2020 Nov 16;134:104693.
        BACKGROUND: Heartland virus (HRTV), a recently reclassified member of the genus Bandavirus, family Phenuiviridae, was first isolated in 2009 from a Missouri farmer exhibiting leukopenia and thrombocytopenia with suspected ehrlichiosis. Since then, more HRTV cases have been diagnosed, and firstline laboratory diagnostic assays are needed to identify future infections Objectives. We sought to develop rapid and reliable IgM and IgG microsphere immunoassays (MIAs) to test sera of patients suspected of having HRTV infection, and to distinguish between recent and past infections. STUDY DESIGN: Heartland virus antigen was captured by an anti-HRTV monoclonal antibody covalently bound to microspheres. Antibodies in human sera from confirmed HRTV-positive and negative cases were reacted with the microsphere complexes and detected using a BioPlex® 200 instrument. Assay cutoffs were determined by receiver operator characteristic analysis of the normalized test output values, equivocal zones for each assay were defined, and sensitivities, specificities, accuracies, and imprecision values were calculated. RESULTS: Sensitivities, specificities and accuracies of the IgM and IgG MIAs were all >95 %. Both tests were precise within and between assay plates, and cross-reactivity with other arboviruses was not observed. CONCLUSIONS: HRTV IgM and IgG MIAs are accurate and rapid first-line methods to serologically identify recent and past HRTV infections.

      2. Subtype diagnosis of sporadic Creutzfeldt-Jakob disease with diffusion MRIexternal icon
        Bizzi A, Pascuzzo R, Blevins J, Moscatelli ME, Grisoli M, Lodi R, Doniselli FM, Castelli G, Cohen ML, Stamm A, Schonberger LB, Appleby BS, Gambetti P.
        Ann Neurol. 2020 Dec 3.
        OBJECTIVE: Sporadic Creutzfeldt-Jakob disease (sCJD) comprises several subtypes as defined by genetic and prion protein characteristics, which are associated with distinct clinical and pathological phenotypes. To date, no clinical test can reliably diagnose the subtype. We established two procedures for the antemortem diagnosis of sCJD subtype using diffusion Magnetic Resonance Imaging (MRI). METHODS: MRI of 1458 patients referred to the National Prion Disease Pathology Surveillance Center were collected through its consultation service. One neuroradiologist blind to the diagnosis scored 12 brain regions and generated a lesion profile. We selected 487 patients with autopsy-confirmed diagnosis of "pure" sCJD subtype and at least one positive diffusion MRI examination. We designed and tested two data-driven procedures for subtype diagnosis: the first procedure -"Prion Subtype Classification Algorithm with MRI" (PriSCA_MRI)- uses only MRI examinations; the second -"PriSCA_MRI+Gen"- includes knowledge of the prion protein codon 129 genotype, a major determinant of sCJD subtypes. Both procedures were tested on first and the last MRI follow-up. RESULTS: PriSCA_MRI classified the three most prevalent subtypes with 82% accuracy. PriSCA_MRI+Gen raised the accuracy to 89% and identified all subtypes. Individually, the two most prevalent sCJD subtypes, MM1 and VV2, were diagnosed with both procedures with accuracies up to 95% and 97%, respectively. The performances of both procedures did not change in 168 patients with longitudinal MRI studies when the last examination was used. INTERPRETATION: This study provides the first practical algorithms for antemortem diagnosis of sCJD subtypes. MRI diagnosis of subtype is likely to be attainable at early disease stages to prognosticate clinical course and design future therapeutic trials. This article is protected by copyright. All rights reserved.

      3. Citrullination-resistant LL-37 is a potent antimicrobial agent in the inflammatory environment high in arginine deiminase activityexternal icon
        Bryzek D, Golda A, Budziaszek J, Kowalczyk D, Wong A, Bielecka E, Shakamuri P, Svoboda P, Pohl J, Potempa J, Koziel J.
        Int J Mol Sci. 2020 Nov 30;21(23).
        LL-37, the only member of the mammalian cathelicidin in humans, plays an essential role in innate immunity by killing pathogens and regulating the inflammatory response. However, at an inflammatory focus, arginine residues in LL-37 can be converted to citrulline via a reaction catalyzed by peptidyl-arginine deiminases (PAD2 and PAD4), which are expressed in neutrophils and are highly active during the formation of neutrophil extracellular traps (NETs). Citrullination impairs the bactericidal activity of LL-37 and abrogates its immunomodulatory functions. Therefore, we hypothesized that citrullination-resistant LL-37 variants would retain the functionality of the native peptide in the presence of PADs. To test this hypothesis, we synthetized LL-37 in which arginine residues were substituted by homoarginine (hArg-LL-37). Bactericidal activity of hArg-LL-37 was comparable with that of native LL-37, but neither treatment with PAD4 nor exposure to NETs affected the antibacterial and immunomodulatory activities of hArg-LL-37. Importantly, the susceptibilities of LL-37 and hArg-LL-37 to degradation by proteases did not significantly differ. Collectively, we demonstrated that citrullination-resistant hArg-LL-37 is an attractive lead compound for the generation of new agents to treat bacterial infections and other inflammatory diseases associated with enhanced PAD activity. Moreover, our results provide a proof-of-concept for synthesis of therapeutic peptides using homoarginine.

      4. Single-step RT-PCR assay for dual genotyping of GI and GII norovirus strainsexternal icon
        Chhabra P, Browne H, Huynh T, Diez-Valcarce M, Barclay L, Kosek MN, Ahmed T, Lopez MR, Pan CY, Vinjé J.
        J Clin Virol. 2020 Nov 18;134:104689.
        BACKGROUND: Noroviruses are the major cause of acute gastroenteritis (AGE) in people of all ages globally. Standardized genotyping is key for outbreak investigations and surveillance networks. OBJECTIVE: Here we describe the validation of a one-step conventional RT-PCR assay for sequence-based dual typing of GI and GII noroviruses. This polymerase (P) and capsid (C) dual typing assay uses a combination of previously published oligonucleotide primers amplifying a genomic region spanning the 3'-end of ORF1 and 5'end of ORF2 resulting in a 579 bp product for GI and 570 bp product for GII viruses. RESULTS: The limit of detection of the assay ranged from 5 to 50 copies of viral RNA per reaction for GI and GII. To validate the assay, we tested 2,663 noroviruspositive stool samples from outbreaks and sporadic cases of AGE in Bangladesh, Guatemala, Peru, and USA collected between 2010-2019, of which 2,392 (90 %) were genotyped successfully. Most of the known genotypes infecting humans (GI (n = 9) and GII (n = 23)) and P types (GI (n = 15), GII, (n = 20)) could be detected. The remaining 270 samples had low viral load (Ct > 30) by real-time RT-PCR. A panel of 166 samples positive for other enteric viruses (rotavirus, astrovirus, sapovirus, adenovirus type 40/41) tested negative. CONCLUSION: The use of broadly reactive genotyping assays greatly strengthens exchange of standardized genotype data globally to monitor trends in genotype diversity which is important for both the development of vaccines and to measure their impact.

      5. Physicochemical characterization and genotoxicity of the broad class of carbon nanotubes and nanofibers used or produced in U.S. facilitiesexternal icon
        Fraser K, Kodali V, Yanamala N, Birch ME, Cena L, Casuccio G, Bunker K, Lersch TL, Evans DE, Stefaniak A, Hammer MA, Kashon ML, Boots T, Eye T, Hubczak J, Friend SA, Dahm M, Schubauer-Berigan MK, Siegrist K, Lowry D, Bauer AK, Sargent LM, Erdely A.
        Part Fibre Toxicol. 2020 Dec 7;17(1):62.
        BACKGROUND: Carbon nanotubes and nanofibers (CNT/F) have known toxicity but simultaneous comparative studies of the broad material class, especially those with a larger diameter, with computational analyses linking toxicity to their fundamental material characteristics was lacking. It was unclear if all CNT/F confer similar toxicity, in particular, genotoxicity. Nine CNT/F (MW #1-7 and CNF #1-2), commonly found in exposure assessment studies of U.S. facilities, were evaluated with reported diameters ranging from 6 to 150 nm. All materials were extensively characterized to include distributions of physical dimensions and prevalence of bundled agglomerates. Human bronchial epithelial cells were exposed to the nine CNT/F (0-24 μg/ml) to determine cell viability, inflammation, cellular oxidative stress, micronuclei formation, and DNA double-strand breakage. Computational modeling was used to understand various permutations of physicochemical characteristics and toxicity outcomes. RESULTS: Analyses of the CNT/F physicochemical characteristics illustrate that using detailed distributions of physical dimensions provided a more consistent grouping of CNT/F compared to using particle dimension means alone. In fact, analysis of binning of nominal tube physical dimensions alone produced a similar grouping as all characterization parameters together. All materials induced epithelial cell toxicity and micronuclei formation within the dose range tested. Cellular oxidative stress, DNA double strand breaks, and micronuclei formation consistently clustered together and with larger physical CNT/F dimensions and agglomerate characteristics but were distinct from inflammatory protein changes. Larger nominal tube diameters, greater lengths, and bundled agglomerate characteristics were associated with greater severity of effect. The portion of tubes with greater nominal length and larger diameters within a sample was not the majority in number, meaning a smaller percentage of tubes with these characteristics was sufficient to increase toxicity. Many of the traditional physicochemical characteristics including surface area, density, impurities, and dustiness did not cluster with the toxicity outcomes. CONCLUSION: Distributions of physical dimensions provided more consistent grouping of CNT/F with respect to toxicity outcomes compared to means only. All CNT/F induced some level of genotoxicity in human epithelial cells. The severity of toxicity was dependent on the sample containing a proportion of tubes with greater nominal lengths and diameters.

      6. Surviving the journey: Comparisons of temperature-stabilizing materials for living arthropod shipmentsexternal icon
        Hunt CM, Benedict MQ, Matilda Collins C, Dotson EM.
        J Am Mosq Control Assoc. 2020 ;36(2):61-65.
        Shipments of living mosquitoes and other arthropods require temperatures that are within a range that is compatible with their health and survival. In addition to express shipping and insulated containers, shipments often include materials that either store heat (i.e., have thermal mass) or otherwise stabilize the temperature. In this paper, we present the results of comparisons of thermal mass and phase change materials to stabilize the temperature under various conditions. We compared a rigid foam refrigerant and a number of phase change materials to bubble wrap for their capacity to moderate temperature change by measuring the temperatures in standard uninsulated shipping containers during exposure to high (37°C), cold (4°C), and freezing (-20°C) temperatures. We make recommendations for shipments depending on the ambient conditions that are expected to be experienced en route.

      7. Development of a subtyping tool for zoonotic pathogen Cryptosporidium canisexternal icon
        Jiang W, Roellig DM, Guo Y, Li N, Feng Y, Xiao L.
        J Clin Microbiol. 2020 Dec 9.
        Cryptosporidium canis is an important cause of cryptosporidiosis in canines and humans. Studies of the transmission characteristics of C. canis are currently hampered by lack of suitable subtyping tools. In this study, we conducted a genomic survey of the pathogen and developed a subtyping tool targeting the partial 60-kDa glycoprotein (gp60) gene. Seventy-six isolates previously identified as C. canis were analyzed using the new subtyping tool. Amplicons of expected size were obtained from 49 isolates, and phylogenetic analysis identified 10 subtypes clustered in five distinct groups (XXa-XXe). The largest group XXa contained 43 isolates from four subtypes that differed slightly from each other at the nucleotide level, while groups XXb-XXe contain one to three isolates each. The similar distribution of subtypes in humans and canines suggests that zoonotic transmission might play an important role in the epidemiology of C. canis In addition, a suspected zoonotic transmission of C. canis between dogs and humans in a household was confirmed using the subtyping tool. The subtyping tool and data generated in this study might improve our understanding of the transmission of this zoonotic pathogen.

      8. BACKGROUND: Isothiazolinones are commonly used preservatives, which may cause allergic contact dermatitis. The Lovibond Isothiazolinone Test Kit (LITK) has been reported to successfully identify clinically relevant, occult isothiazolinones in patient personal care products. OBJECTIVE: The aim of the study was to analyze dish soaps and personal care products that do not declare isothiazolinones ("no-ISO") for the presence of isothiazolinones via 2 methods: LITK and ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). METHODS: No-ISO dish soaps (n = 9), a convenience sample of patient products (n = 6), and controls (positive [isothiazolinone declared], n = 5; negative, n = 2) were tested with LITK (X3) and UHPLC-MS/MS. RESULTS: Several no-ISO dish soaps and personal products were positive for isothiazolinones (LITK, n = 12; UHPLC-MS/MS, n = 3). Ultrahigh-performance liquid chromatography-tandem mass spectrometry specifically identified methylisothiazolinone alone in 1 no-ISO dish soap, methylchloroisothiazolinone in another, and both in a third. Using UHPLC-MS/MS as the criterion standard, we observed the accuracy of LITK for 9 dish soaps was poor (sensitivity, 66.7%; specificity, 20%) and very poor for 6 personal care products (sensitivity, 0%; specificity, 0%). CONCLUSIONS: Personal products may contain undeclared isothiazolinones. The current study found that LITK had poor accuracy for testing dish soap and personal care products. Clinicians should be aware of these factors when managing patients with contact allergy to isothiazolinones.

      9. Formaldehyde release from predispersed tattoo inks: Analysis using the chromotropic acid methodexternal icon
        Liou YL, Voller LM, Liszewski W, Ericson ME, Siegel PD, Warshaw EM.
        Dermatitis. 2020 Dec 1.
        BACKGROUND: Allergic contact dermatitis to tattoo ink may last from weeks to years. Formaldehyde is a strong sensitizer that may be present in predispersed tattoo inks. OBJECTIVES: The aim of this study was to evaluate the presence of formaldehyde in predispersed tattoo inks using the chromotropic acid method. METHODS: Tattoo inks from 39 companies were evaluated. Inclusion criteria included availability to purchase inks online through US tattoo product wholesalers or individual Web sites. Brands were grouped based on prevalence of use: common, uncommon, or rare. For common brands, 8 colors (primary colors, secondary colors, black, and white) were purchased. For uncommon and rare brands, 5 colors (primary colors, black, and white) were purchased. Each ink was tested with standard chromotropic acid method procedures; concentration of formaldehyde released was quantified using spectrophotometry. RESULTS: In total, 127 tattoo inks were purchased and tested. Ninety-three (73%) tested positive for formaldehyde release; 34 (27%) tested negative. Formaldehyde release did not correlate with color or brand. At least 1 ink from all brands (except 1) was positive for formaldehyde release. CONCLUSION: Approximately three-quarters of selected US tattoo inks tested positive for formaldehyde release. Clinicians should be aware of tattoo ink as a potential source of formaldehyde.

      10. Primary swine respiratory epithelial cell lines for the efficient isolation and propagation of influenza A virusesexternal icon
        Meliopoulos V, Cherry S, Wohlgemuth N, Honce R, Barnard K, Gauger P, Davis T, Shult P, Parrish C, Schultz-Cherry S.
        J Virol. 2020 Nov 23;94(24).
        Influenza virus isolation from clinical samples is critical for the identification and characterization of circulating and emerging viruses. Yet efficient isolation can be difficult. In these studies, we isolated primary swine nasal and tracheal respiratory epithelial cells and immortalized swine nasal epithelial cells (siNEC) and tracheal epithelial cells (siTEC) that retained the abilities to form tight junctions and cilia and to differentiate at the air-liquid interface like primary cells. Critically, both human and swine influenza viruses replicated in the immortalized cells, which generally yielded higher-titer viral isolates from human and swine nasal swabs, supported the replication of isolates that failed to grow in Madin-Darby canine kidney (MDCK) cells, and resulted in fewer dominating mutations during viral passaging than MDCK cells.IMPORTANCE Robust in vitro culture systems for influenza virus are critically needed. MDCK cells, the most widely used cell line for influenza isolation and propagation, do not adequately model the respiratory tract. Therefore, many clinical isolates, both animal and human, are unable to be isolated and characterized, limiting our understanding of currently circulating influenza viruses. We have developed immortalized swine respiratory epithelial cells that retain the ability to differentiate and can support influenza replication and isolation. These cell lines can be used as additional tools to enhance influenza research and vaccine development.

      11. Analysis of recombinant proteins for Q fever diagnosticsexternal icon
        Miller HK, Kersh GJ.
        Sci Rep. 2020 Dec 1;10(1):20934.
        Serology is essential for Q fever diagnostics, a disease caused by the bacterial pathogen Coxiella burnetii. The gold standard test is an immunofluorescence assay utilizing whole cell antigens, which are both dangerous and laborious to produce. Complexities of the antigen coupled with the subjective nature of the assay lead to decreased uniformity of test results and underscore the need for improved methodologies. Thirty-three C. burnetii proteins, previously identified as immunoreactive, were screened for reactivity to naturally infected goat serum. Based on reactivity, 10 proteins were analyzed in a secondary screen against human serum from healthy donors. Assay sensitivity and specificity ranged from 21 to 71% and 90 to 100%, respectively. Three promising antigens were identified based on receiver operating characteristic curve analysis (CBU_1718, CBU_0307, and CBU_1398). Five multiplex assays failed to outperform the individual proteins, with sensitivities and specificities ranging from 29 to 57% and 90 to 100%, respectively. Truncating the top antigen, CBU_1718, had no effect on specificity (90%); yet sensitivity decreased dramatically (71% to 21%). Through this study, we have expanded the subset of C. burnetii immunoreactive proteins validated by enzyme-linked immunosorbent assay and demonstrate the effect of novel antigen combinations and protein truncations on assay performance.

      12. Evolution and rapid spread of a reassortant A(H3N2) virus that predominated the 2017-2018 influenza seasonexternal icon
        Potter BI, Kondor R, Hadfield J, Huddleston J, Barnes J, Rowe T, Guo L, Xu X, Neher RA, Bedford T, Wentworth DE.
        Virus Evol. 2019 Jul;5(2):vez046.
        The 2017-2018 North American influenza season caused more hospitalizations and deaths than any year since the 2009 H1N1 pandemic. The majority of recorded influenza infections were caused by A(H3N2) viruses, with most of the virus's North American diversity falling into the A2 clade. Within A2, we observe a subclade which we call A2/re that rose to comprise almost 70 per cent of A(H3N2) viruses circulating in North America by early 2018. Unlike most fast-growing clades, however, A2/re contains no amino acid substitutions in the hemagglutinin (HA) segment. Moreover, hemagglutination inhibition assays did not suggest substantial antigenic differences between A2/re viruses and viruses sampled during the 2016-2017 season. Rather, we observe that the A2/re clade was the result of a reassortment event that occurred in late 2016 or early 2017 and involved the combination of the HA and PB1 segments of an A2 virus with neuraminidase (NA) and other segments a virus from the clade A1b. The success of this clade shows the need for antigenic analysis that targets NA in addition to HA. Our results illustrate the potential for non-HA drivers of viral success and necessitate the need for more thorough tracking of full viral genomes to better understand the dynamics of influenza epidemics.

      13. AcanR3990 qPCR: a novel, highly sensitive, bioinformatically-informed assay to detect Angiostrongylus cantonensis infectionsexternal icon
        Sears WJ, Qvarnstrom Y, Dahlstrom E, Snook K, Kaluna L, Baláž V, Feckova B, Šlapeta J, Modry D, Jarvi S, Nutman TB.
        Clin Infect Dis. 2020 Nov 30.
        BACKGROUND: Angiostrongylus cantonensis (Ac), or the rat lungworm, is a major cause of eosinophilic meningitis. Humans are infected by ingesting the 3 rd stage larvae from primary hosts, snails and slugs, or paratenic hosts. The currently used molecular test is a qPCR assay targeting the ITS1 rDNA region (ITS1) of Ac. METHODS: In silico design of a more sensitive qPCR assay was performed based on tandem repeats predicted to be the most abundant by the RepeatExplorer algorithm. Genomic DNA (gDNA) of Ac were used to determine the analytical sensitivity and specificity of the best primer/probe combination. This assay was then applied to clinical and environmental samples. RESULTS: The limit of detection of the best performing assay, AcanR3990, was 1 fg (the DNA equivalent of 1/100,000 dilution of a single 3 rd stage larvae). Out of 127 CDC archived CSF samples from varied geographic locations, the AcanR3990 qPCR detected the presence of Ac in 49/49 ITS1 confirmed angiostrongyliasis patients along with 15/73 samples previously negative by ITS1 qPCR despite strong clinical suspicion for angiostrongyliasis. Intermediate hosts (gastropods) and an accidental host, a symptomatic horse, were also tested with similar improvement in detection observed. AcanR3990 qPCR did not cross-react in five CSF from patients with proven neurocysticercosis, toxocariasis, gnathostomiasis and baylisascariasis. AcanR3990 qPCR failed to amplify genomic DNA from the other related Angiostrongylus species tested except for A. mackerrasae (Am), a neurotropic species limited to Australia that would be expected to present with a clinical syndrome indistinguishable from Ac. CONCLUSION: These results suggest AcanR3990 qPCR assay is highly sensitive and specific with potential wide applicability as a One Health detection method for Ac and Am.

    • Maternal and Child Health
      1. Prevalence of intellectual disability among eight-year-old children from selected communities in the United States, 2014external icon
        Patrick ME, Shaw KA, Dietz PM, Baio J, Yeargin-Allsopp M, Bilder DA, Kirby RS, Hall-Lande JA, Harrington RA, Lee LC, Lopez ML, Daniels J, Maenner MJ.
        Disabil Health J. 2020 Nov 15:101023.
        BACKGROUND: Children with intellectual disability (ID), characterized by impairments in intellectual functioning and adaptive behavior, benefit from early identification and access to services. Previous U.S. estimates used administrative data or parent report with limited information for demographic subgroups. OBJECTIVE: Using empiric measures we examined ID characteristics among 8-year-old children and estimated prevalence by sex, race/ethnicity, geographic area and socioeconomic status (SES) area indicators. METHODS: We analyzed data for 8-year-old children in 9 geographic areas participating in the 2014 Autism and Developmental Disabilities Monitoring Network. Children with ID were identified through record review of IQ test data. Census and American Community Survey data were used to estimate the denominator. RESULTS: Overall, 11.8 per 1,000 (1.2%) had ID (IQ ≤ 70), of whom 39% (n = 998) also had autism spectrum disorder. Among children with ID, 1,823 had adaptive behavior test scores for which 64% were characterized as impaired. ID prevalence per 1,000 was 15.8 (95% confidence interval [95% CI], 15.0-16.5) among males and 7.7 (95% CI, 7.2-8.2) among females. ID prevalence was 17.7 (95% CI, 16.6-18.9) among children who were non-Hispanic black; 12.0 (95% CI, 11.1-13.0), among Hispanic; 8.6 (95% CI, 7.1-10.4), among non-Hispanic Asian; and 8.0 (95% CI, 7.5-8.6), among non-Hispanic white. Prevalence varied across geographic areas and was inversely associated with SES. CONCLUSIONS: ID prevalence varied substantively among racial, ethnic, geographic, and SES groups. Results can inform strategies to enhance identification and improve access to services particularly for children who are minorities or living in areas with lower SES.

      2. Prevalence and mortality in children with congenital diaphragmatic hernia: A multi-country studyexternal icon
        Politis MD, Bermejo-Sánchez E, Canfield MA, Contiero P, Cragan JD, Dastgiri S, de Walle HE, Feldkamp ML, Nance A, Groisman B, Gatt M, Benavides-Lara A, Hurtado-Villa P, Kallén K, Landau D, Lelong N, Lopez-Camelo J, Martinez L, Morgan M, Mutchinick OM, Pierini A, Rissmann A, Šípek A, Szabova E, Wertelecki W, Zarante I, Bakker MK, Kancherla V, Mastroiacovo P, Nembhard WN.
        Ann Epidemiol. 2020 Nov 27.
        PURPOSE: This study determined the prevalence, mortality and time trends of children with congenital diaphragmatic hernia (CDH). METHODS: Twenty-five hospital- and population-based surveillance programs in 19 International Clearinghouse for Birth Defects Surveillance and Research member countries provided birth defects mortality data between 1974 and 2015. CDH cases included live births, stillbirths, or elective termination of pregnancy for fetal anomalies. Prevalence, cumulative mortality rates, and 95% confidence intervals (CI) were calculated using Poisson regression and Kaplan-Meier product-limit method. Joinpoint regression analyses were conducted to assess time trends. RESULTS: The prevalence of CDH was 2.6 per 10,000 total births (95% CI: 2.5-2.7), slightly increasing between 2001 and 2012 (average annual percent change [AAPC] = 0.5%; 95% CI:-0.6-1.6). The total percent mortality of CDH was 37.7%, with hospital-based registries having more deaths among live births than population-based registries (45.1% vs. 33.8%). Mortality rates decreased over time (AAPC = -2.4%; 95% CI: -3.8--1.1). Most deaths due to CDH occurred among 2- to 6-day-old infants for both registry types (36.3%, hospital-based; 12.1%, population-based). CONCLUSION: The mortality of CDH has decreased over time. Mortality remains high during the first week and varied by registry type.

      3. Late-onset hearing loss from congenital cytomegalovirus infection after newborn period in a highly immune population in Chinaexternal icon
        Wang C, Liu X, Wang S, Zhang W, Wang H, Ma W, Meng X, Xu X, Li Z, Pan Q, Zhang S, Wang P, Lin Q, Wang X, Amin M, Dollard S, Xu A, Chung W.
        Pediatr Infect Dis J. 2021 Jan;40(1):70-73.
        After following 141 children with likely asymptomatic congenital cytomegalovirus infection in a highly immune population in China, four children (2.8%) were found to have late-onset hearing loss. No maternal or childhood factors, except higher saliva cytomegalovirus viral load at birth (P = 0.03), were associated with increased risk of developing a hearing loss.

    • Occupational Safety and Health
      1. BACKGROUND: The use of helmets was considered to be one of the important prevention strategies employed on construction sites. The shock absorption performance of a construction (or industrial) helmet is its most important performance parameter. Industrial helmets will experience cumulative structural damage when being impacted repeatedly with impact magnitudes greater than its endurance limit. OBJECTIVE: The current study is to test if the shock absorption performance of Type I construction helmets subjected to repeated impacts can be improved by applying polyethylene air-bubble cushions to the helmet suspension system. METHODS: Drop impact tests were performed using a commercial drop tower test machine following the ANSI Z89.1 Type I drop impact protocol. Typical off-the-shelf Type I construction helmets were evaluated in the study. A 5 mm thick air-bubble cushioning liner was placed between the headform and the helmet to be tested. Helmets were impacted ten times at different drop heights from 0.61 to 1.73 m. The effects of the air-bubble cushioning liner on the helmets' shock absorption performance were evaluated by comparing the peak transmitted forces collected from the original off-the-shelf helmet samples to the helmets equipped with air-bubble cushioning liners. RESULTS: Our results showed that a typical Type I construction helmet can be subjected to repeated impacts with a magnitude less than 22 J (corresponding to a drop height 0.61 m) without compromising its shock absorption performance. In comparison, the same construction helmet, when equipped with an air-bubble cushioning liner, can be subjected to repeated impacts of a magnitude of 54 J (corresponding to a drop height 1.52 m) without compromising its shock absorption performance. CONCLUSIONS: The results indicate that the helmet's shock absorbing endurance limit has been increased by 145% with addition of an air-bubble cushioning liner.

      2. Speech intelligibility test methodology applied to powered air-purifying respirators used in healthcareexternal icon
        Xu S, Simons J, Yorio P, Rottach D, Zhuang Z, Radonovich L.
        J Occup Environ Hyg. 2020 Dec 7:1-11.
        Powered air-purifying respirators (PAPRs) are worn to protect workers from hazardous respiratory exposures in a wide range of workplaces, including healthcare. However, PAPRs may diminish the ability of wearers to correctly hear words spoken by others, potentially interfering with safe performance of healthcare duties. Accordingly, the impact of PAPRs during healthcare use on speech intelligibility (SI) and consequently on user safety, usability, and patient care is not well studied. The objectives of this study were to (1) determine a listener's ability to comprehend single-syllable words spoken by a PAPR wearer; (2) determine a PAPR wearer's ability to intelligibly hear and identify single-syllable words spoken by a PAPR wearer; (3) to assess the variability between speakers, listeners, and PAPR models; (4) to investigate the effects of PAPR design features on SI; and (5) inform a SI requirement for certifying future PAPRs for use in healthcare. This study utilized a Modified Rhyme Test to assess SI for PAPRs. The current National Institute for Occupational Safety and Health (NIOSH) methods for assessing SI are limited to the recently introduced PAPR100 respirator class and the class of respirators claiming chemical, biological, radiological, and nuclear (CBRN) protections. Four NIOSH-approved PAPRs were evaluated using four human subjects. Four experimental conditions were examined:(1) Speaker and Listener with no PAPR; (2) Speaker and Listener both wearing PAPRs; (3) Speaker with a PAPR, Listener without a PAPR; and (4) Speaker without a PAPR, Listener with a PAPR resulted in a total of 144 experiments. Statistical analysis showed that the SI performance ratings were not significantly different among the PAPR models, but experimental conditions had significant impact on SI. The pattern of SI across the conditions of the experiment also showed a significant difference depending on PAPR model. The SI performance rating for all PAPRs could meet the current NIOSH CBRN certification requirement for speech intelligibility.

      3. BACKGROUND: Transportation events are the most common cause of offshore fatalities in the oil and gas industry, of which helicopter accidents comprise the majority. Little is known about injury distributions in civilian helicopter crashes, and knowledge of injury distributions could focus research and recommendations for enhanced injury prevention and post-crash survival. This study describes the distribution of injuries among fatalities in Gulf of Mexico oil and gas industry-related helicopter accidents, provides a detailed injury classification to identify potential areas of enhanced safety design, and describes relevant safety features for mitigation of common injuries. METHODS: Decedents of accidents during 2004-2014 were identified, and autopsy reports were requested from responsible jurisdictions. Documented injuries were coded using the Abbreviated Injury Scale (AIS), and frequency and proportion of injuries by AIS body region and severity were calculated. Injuries were categorized into detailed body regions to target areas for prevention. RESULTS: A total of 35 autopsies were coded, with 568 injuries documented. Of these, 23.4% were lower extremity, 22.0% were thorax, 13.6% were upper extremity, and 13.4% were face injuries. Minor injuries were most prevalent in the face, neck, upper and lower extremities, and abdomen. Serious or worse injuries were most prevalent in the thorax (53.6%), spine (50.0%), head (41.7%), and external/other regions (75.0%). The most frequent injuries by detailed body regions were thoracic organ (23.0%), thoracic skeletal (13.3%), abdominal organ (9.6%), and leg injuries (7.4%). Drowning occurred in 13 (37.1%) of victims, and drowning victims had a higher proportion of moderate brain injuries (7.8%) and lower number of documented injuries (3.8) compared with non-drowning victims (2.9 and 9.4%, respectively). CONCLUSIONS: Knowledge of injury distributions focuses and prioritizes the need for additional safety features not routinely used in helicopters. The most frequent injuries occurred in the thorax and lower extremity regions. Future research requires improved and expanded data, including collection of detailed data to allow characterization of both injury mechanism and distribution. Improved safety systems including airbags and helmets should be implemented and evaluated for their impact on injuries and fatalities.

    • Occupational Safety and Health - Mining
      1. Application of a convolutional neural network for seismic phase picking of mining-induced seismicityexternal icon
        Johnson SW, Chambers DJ, Boltz MS, Koper KD.
        Geophys J Int. 2021 ;224(1):230-240.
        Monitoring mining-induced seismicity (MIS) can help engineers understand the rock mass response to resource extraction. With a thorough understanding of ongoing geomechanical processes, engineers can operate mines, especially those mines with the propensity for rockbursting, more safely and efficiently. Unfortunately, processing MIS data usually requires significant effort from human analysts, which can result in substantial costs and time commitments. The problem is exacerbated for operations that produce copious amounts of MIS, such as mines with high-stress and/or extraction ratios. Recently, deep learning methods have shown the ability to significantly improve the quality of automated arrival-time picking on earthquake data recorded by regional seismic networks. However, relatively little has been published on applying these techniques to MIS. In this study, we compare the performance of a convolutional neural network (CNN) originally trained to pick arrival times on the Southern California Seismic Network (SCSN) to that of human analysts on coal-mine-related MIS. We perform comparisons on several coal-related MIS data sets recorded at various network scales, sampling rates and mines. We find that the Southern-California-trained CNN does not perform well on any of our data sets without retraining. However, applying the concept of transfer learning, we retrain the SCSN model with relatively little MIS data after which the CNN performs nearly as well as a human analyst. When retrained with data from a single analyst, the analyst-CNN pick time residual variance is lower than the variance observed between human analysts. We also compare the retrained CNN to a simpler, optimized picking algorithm, which falls short of the CNN's performance. We conclude that CNNs can achieve a significant improvement in automated phase picking although some data set-specific training will usually be required. Moreover, initializing training with weights found from other, even very different, data sets can greatly reduce the amount of training data required to achieve a given performance threshold.

      2. Monitoring of multiple-level stress interaction at two underground limestone minesexternal icon
        Slaker B, Murphy M, Rashed G, Gangrade V, Van Dyke M, Minoski T, Floyd K.
        Min Metall Explor. 2020 .
        The National Institute for Occupational Safety and Health (NIOSH) has previously established pillar design guidelines for shallow, flat-lying mines and single-level operations. Little guidance exists for ground control design in multiple-level stone mines, and understanding the interactions between levels would allow engineers to better select interburden thicknesses and the necessary amount of pillar columnization. To investigate these loading conditions in multiple-level environments, NIOSH has partnered with two separately operated multiple-level mines to study the stress interaction between the levels as undermining occurs. The first mine is located in Tennessee with up to a 243-m overburden and 7-m interburden thickness between levels. The second mine is located in Kentucky with a 304-m overburden and 26-m interburden thickness between levels. The monitoring program at these sites includes stressmeters and LiDAR for tracking stress redistributions and rock displacement in response to undermining. Monitoring is ongoing, but numerical modeling results show the expected interaction between levels.

    • Parasitic Diseases
      1. Efficacy of extended release formulations of Natular™ (spinosad) against larvae and adults of Anopheles mosquitoes in western Kenyaexternal icon
        Gimnig JE, Ombok M, Bayoh N, Mathias D, Ochomo E, Jany W, Walker ED.
        Malar J. 2020 Nov 26;19(1):436.
        BACKGROUND: Larval source management is recommended as a supplementary vector control measure for the prevention of malaria. Among the concerns related to larviciding is the feasibility of implementation in tropical areas with large numbers of habitats and the need for frequent application. Formulated products of spinosad that are designed to be effective for several weeks may mitigate some of these concerns. METHODS: In a semi-field study, three formulations of spinosad (emulsifiable concentrate, extended release granules and tablet formulations) were tested in naturalistic habitats in comparison to an untreated control. Cohorts of third instar Anopheles gambiae (Diptera: Culicidae) were introduced into the habitats in screened cages every week up to four weeks after application and monitored for survivorship over three days. A small-scale field trial was then conducted in two villages. Two of the spinosad formulations were applied in one village over the course of 18 months. Immature mosquito populations were monitored with standard dippers in sentinel sites and adult populations were monitored by pyrethrum spray catches. RESULTS: In the semi-field study, the efficacy of the emulsifiable concentrate of spinosad waned 1 week after treatment. Mortality in habitats treated with the extended release granular formulation of spinosad was initially high but declined gradually over 4 weeks while mortality in habitats treated with the dispersable tablet formulation was low immediately after treatment but rose to 100% through four weeks. In the field study, immature and adult Anopheles mosquito populations were significantly lower in the intervention village compared to the control village during the larviciding period. Numbers of collected mosquitoes were lower in the intervention village compared to the control village during the post-intervention period but the difference was not statistically significant. CONCLUSIONS: The extended release granular formulation and the dispersible tablet formulations of spinosad are effective against larval Anopheles mosquitoes for up to four weeks and may be an effective tool as part of larval source management programmes for reducing adult mosquito density and malaria transmission.

      2. Advancing malaria prevention and control in africa through the Peace Corps-US President's Malaria Initiative Partnershipexternal icon
        Henderson SJ, Belemvire A, Nelson R, Linn A, Moriarty LF, Brofsky E, Diaw M, Gittelman D.
        Glob Adv Health Med. 2020 ;9.
        Background: Peace Corps is a US government volunteer service agency which provides trained Volunteers to assist host countries in addressing critical development challenges at the community level. The US President's Malaria Initiative provides technical expertise and financial resources to reduce malaria morbidity and mortality in focus countries in sub-Saharan Africa. Objective(s): We aim to describe the nature of the collaboration between Peace Corps and President's Malaria Initiative (PMI) and highlight examples of the partnership in select countries. Method(s): We conducted an analysis of retrospective data obtained from Peace Corps and PMI for the years 2014-2019. Result(s): Volunteers were able to learn about and work on malaria prevention and control with PMI in three key ways: a malaria-specific training program for staff and Volunteers; malaria-focused small grants; and extension of Volunteer assignments for a third year to support malaria projects. Successful Peace Corps projects supported by PMI, at the community level, were highlighted, with a focus on Rwanda, Benin, Zambia, Madagascar, and Senegal. In Fiscal Year 2019, 1408 Volunteers contributed to malaria prevention activities in 18 Peace Corps programs across Africa, of which 15 were PMI focus countries. While the majority of documented work by Volunteers has involved social and behavior change, there were many other ways to partner with PMI staff. Conclusion(s): Each of the proven interventions that PMI supports for malaria prevention and control may have a role for Volunteer involvement. Combined with the technical expertise and the relationships that PMI staff have with national-level counterparts in PMI focus countries, the continued collaboration between Peace Corps and PMI can accelerate the fight against malaria.

      3. Evaluation of a single screen and treat strategy to detect asymptomatic malaria among pregnant women from selected health facilities in Lindi region, Tanzaniaexternal icon
        Kitojo C, Chacky F, Kigadye ES, Mugasa JP, Lusasi A, Mohamed A, Walker P, Reaves EJ, Gutman JR, Ishengoma DS.
        Malar J. 2020 Nov 30;19(1):438.
        BACKGROUND: In areas of high transmission, malaria in pregnancy (MiP) primarily causes asymptomatic infections; these infections nonetheless increase the risk of adverse maternal and fetal outcomes. In 2014, Tanzania initiated a single screening and treatment (SST) strategy for all pregnant women at their first antenatal care (ANC) visit using malaria rapid diagnostic tests (RDT) for surveillance purposes. However, there is paucity of data on the effectiveness of SST in the prevention of MiP. The objective of this study was to estimate the number of asymptomatic infections among pregnant women detected by SST, which would have been missed in the absence of the policy. METHODS: Data from pregnant women attending their first ANC visits between October 2017 and June 2018, including gestational age, history of fever, and RDT results, were abstracted from ANC registers in eight health centres in two randomly selected districts, Kilwa and Lindi, in Lindi Region. The proportion of symptomatic (with history of fever in the past 48 h) and asymptomatic pregnant women with positive RDTs were calculated and stratified by trimester (first, second and third). The study areas were categorized as low transmission with prevalence < 10% or moderate/high with ≥ 10%. RESULTS: Over the study period, 1,845 women attended their first ANC visits; 22.1% were in the first trimester (< 12 weeks gestation age). Overall 15.0% of the women had positive RDTs, and there was a trend towards higher malaria prevalence in the first (15.9%) and second (15.2%) trimesters, compared to the third (7.1%), although the differences were not statistically significant (p = 0.07). In total, 6.9% of women reported fever within the past 48 h and, of these, 96.1% were RDT positive. For every 100 pregnant women in the moderate/high and low transmission areas, SST identified 60 and 26 pregnant women, respectively, with asymptomatic infections that would have otherwise been missed. Among the 15.9% of women detected in the first trimester, 50.7% were asymptomatic. CONCLUSION: In areas of moderate/high transmission, many infected women were asymptomatic, and would have been missed in the absence of SST. The benefits on maternal and fetal birth outcomes of identifying these infections depend heavily on the protection afforded by treatment, which is likely to be greatest for women presenting in the first trimester when intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) is contraindicated, and in areas with high SP resistance, such as most parts of Tanzania. An evaluation of the impact and cost-effectiveness of SST across different transmission strata is warranted.

      4. Susceptibility of Anopheles gambiae from Côte d'Ivoire to insecticides used on insecticide-treated nets: evaluating the additional entomological impact of piperonyl butoxide and chlorfenapyrexternal icon
        Kouassi BL, Edi C, Tia E, Konan LY, Akré MA, Koffi AA, Ouattara AF, Tanoh AM, Zinzindohoue P, Kouadio B, Andre M, Irish SR, Armistead J, Dengela D, Cissé NG, Flatley C, Chabi J.
        Malar J. 2020 Dec 9;19(1):454.
        BACKGROUND: Pyrethroid-treated mosquito nets are currently the mainstay of vector control in Côte d'Ivoire. However, resistance to pyrethroids has been reported across the country, limiting options for insecticide resistance management due to the paucity of alternative insecticides. Two types of insecticide-treated nets (ITNs), ITNs with pyrethroids and the synergist piperonyl butoxide (PBO), and Interceptor®G2 nets, a net treated with a combination of chlorfenapyr and alpha-cypermethrin, are believed to help in the control of pyrethroid-resistant mosquitoes. METHODS: The susceptibility of Anopheles gambiae sensu lato (s.l.) to pyrethroid insecticides with and without pre-exposure to PBO as well as to chlorfenapyr was investigated in fifteen sites across the country. Susceptibility tests were conducted on 2- to 4-day old adult female An. gambiae s.l. reared from larval collections. The resistance status, intensity, and effects of PBO on mortality after exposure to different concentrations of deltamethrin, permethrin and alpha-cypermethrin were determined using WHO susceptibility test kits. In the absence of a WHO-recommended standard protocol for chlorfenapyr, two interim doses (100 and 200 µg/bottle) were used to test the susceptibility of mosquitoes using the CDC bottle assay method. RESULTS: Pre-exposure to PBO did not result in full restoration of susceptibility to any of the three pyrethroids for the An. gambiae s.l. populations from any of the sites surveyed. However, PBO pre-exposure did increase mortality for all three pyrethroids, particularly deltamethrin (from 4.4 to 48.9%). Anopheles gambiae s.l. from only one site (Bettie) were susceptible to chlorfenapyr at the dose of 100 µg active ingredient (a.i.)/bottle. At the dose of 200 µg (a.i.)/bottle, susceptibility was only recorded in 10 of the 15 sites. CONCLUSION: Low mosquito mortality was found for pyrethroids alone, and while PBO increased mortality, it did not restore full susceptibility. The vector was not fully susceptible to chlorfenapyr in one third of the sites tested. However, vector susceptibility to chlorfenapyr seems to be considerably higher than for pyrethroids alone or with PBO. These data should be used cautiously when making ITN procurement decisions, noting that bioassays are conducted in controlled conditions and may not fully represent field efficacy where the host-seeking behaviours, which include free-flying activity are known to enhance pro-insecticide chlorfenapyr intoxication to mosquitoes.

      5. Malaria chemoprevention in the postdischarge management of severe anemiaexternal icon
        Kwambai TK, Dhabangi A, Idro R, Opoka R, Watson V, Kariuki S, Kuya NA, Onyango ED, Otieno K, Samuels AM, Desai MR, Boele van Hensbroek M, Wang D, John CC, Robberstad B, Phiri KS, Ter Kuile FO.
        N Engl J Med. 2020 Dec 3;383(23):2242-2254.
        BACKGROUND: Children who have been hospitalized with severe anemia in areas of Africa in which malaria is endemic have a high risk of readmission and death within 6 months after discharge. No prevention strategy specifically addresses this period. METHODS: We conducted a multicenter, two-group, randomized, placebo-controlled trial in nine hospitals in Kenya and Uganda to determine whether 3 months of malaria chemoprevention could reduce morbidity and mortality after hospital discharge in children younger than 5 years of age who had been admitted with severe anemia. All children received standard in-hospital care for severe anemia and a 3-day course of artemether-lumefantrine at discharge. Two weeks after discharge, children were randomly assigned to receive dihydroartemisinin-piperaquine (chemoprevention group) or placebo, administered as 3-day courses at 2, 6, and 10 weeks after discharge. Children were followed for 26 weeks after discharge. The primary outcome was one or more hospital readmissions for any reason or death from the time of randomization to 6 months after discharge. Conditional risk-set modeling for recurrent events was used to calculate hazard ratios with the use of the Prentice-Williams-Peterson total-time approach. RESULTS: From May 2016 through May 2018, a total of 1049 children underwent randomization; 524 were assigned to the chemoprevention group and 525 to the placebo group. From week 3 through week 26, a total of 184 events of readmission or death occurred in the chemoprevention group and 316 occurred in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.54 to 0.78; P<0.001). The lower incidence of readmission or death in the chemoprevention group than in the placebo group was restricted to the intervention period (week 3 through week 14) (hazard ratio, 0.30; 95% CI, 0.22 to 0.42) and was not sustained after that time (week 15 through week 26) (hazard ratio, 1.13; 95% CI, 0.87 to 1.47). No serious adverse events were attributed to dihydroartemisinin-piperaquine. CONCLUSIONS: In areas with intense malaria transmission, 3 months of postdischarge malaria chemoprevention with monthly dihydroartemisinin-piperaquine in children who had recently received treatment for severe anemia prevented more deaths or readmissions for any reason after discharge than placebo. (Funded by the Research Council of Norway and the Centers for Disease Control and Prevention; number, NCT02671175.).

      6. Investigation of dracunculiasis transmission among humans, Chad, 2013-2017external icon
        Liu EW, Sircar AD, Matchanga K, Mahamat AM, Ngarhor N, Ouakou PT, Zirimwabagabo H, Ruiz-Tiben E, Sankara D, Wiegand R, Roy SL.
        Am J Trop Med Hyg. 2020 Dec 7.
        Dracunculiasis, slated for global eradication, typically is acquired by drinking stagnant water containing microscopic crustaceans (copepods) infected with Dracunculus medinensis larvae, causing clusters of case persons with worms emerging from the skin. Following a 10-year absence of reported cases, 9-17 sporadic human cases with few epidemiologic links have been reported annually in Chad since 2010; dog infections have also been reported since 2012. We conducted an investigation of human cases in Chad to identify risk factors. We conducted a case-control study using a standardized questionnaire to assess water and aquatic animal consumption, and links to dog infections. Case persons had laboratory-confirmed D. medinensis during 2013-2017. Each case person was matched to one to three controls without history of disease by age, gender, and residency in the village where the case person was likely infected. We estimated odds ratios (ORs) using simple conditional logistic regression. We enrolled 25 case persons with 63 matched controls. Dracunculiasis was associated with consumption of untreated water from hand-dug wells (OR: 13.4; 95% CI: 1.7-108.6), but neither with consumption of aquatic animals nor presence of infected dogs in villages. Unsafe water consumption remains associated with dracunculiasis. Education of populations about consuming safe water and using copepod filters to strain unsafe water should continue and expand, as should efforts to develop and maintain safe drinking water sources. Nevertheless, the peculiar epidemiology in Chad remains incompletely explained. Future studies of dogs might identify other risk factors.

      7. Certifying Guinea worm eradication: current challengesexternal icon
        Molyneux DH, Eberhard ML, Cleaveland S, Addey R, Guiguemdé RT, Kumar A, Magnussen P, Breman JG.
        Lancet. 2020 Dec 5;396(10265):1857-1860.

    • Program Evaluation
      1. OBJECTIVE: A cross-case analysis was used to discover how two states benefitted from expanded use of evaluation for asthma quality improvement initiatives. If an asthma quality improvement (QI) initiative is successfully evaluated, data can inform how to effectively integrate clinical practice guidelines and circumvent non-clinical reasons that interrupt QI projects such as low staff interest. This article addresses a gap in the literature on quality of evaluation support needed to improve and sustain asthma QI at local health care organizations by describing the similar discoveries observed at two independent QI statewide initiatives in State 1 and State 2. METHODS: As part of a larger review, two states funded by the National Prevention Organization (NPO) were identified based on similarities in evaluation approaches. Each state used an iterative stakeholder driven evaluation approach, mixed methods, process evaluation indicators, and active use of evaluation findings. The asthma QI initiatives and evaluations in State 1 and State 2 were coordinated independent of each other. RESULTS: Although both states found that asthma QI initiatives improved health outcomes, evaluation data were able to further pinpoint areas that would improve quality of technical support to health care organizations and identify markers of sustainability, such as non-traditional benefits to staff, and intervention sites. CONCLUSION: Findings suggest that when evaluation is used to guide implementation, data are available to develop site-specific assistance and identify sustainability markers to prevent interruption of positive health outcomes associated with an asthma QI initiative.

    • Reproductive Health
      1. PURPOSE: This study aimed to evaluate the receipt of chlamydia and gonorrhea screening among women aged 15-24 years undergoing long-acting reversible contraception (LARC) insertion. METHODS: We used the 2016-2017 MarketScan commercial claims data set to identify sexually active women aged 15-24 years with LARC insertion in 2017 and had ≥12 months of insurance coverage before the date of LARC insertion. Sexual activity (defined by Healthcare Effectiveness Data and Information Set chlamydia testing measure) and LARC insertion, including intrauterine device (IUD) and implant insertion, were identified by applicable International Classification of Disease, Tenth Revision, Healthcare Common Procedure Coding System, and Current Procedural Terminology codes. We evaluated chlamydia and gonorrhea testing performed in the preceding 12 months or at the time of LARC insertion among sexually active women aged 15-24 years. RESULTS: We identified 37,331sexually active women aged 15-24 years with LARC insertion. Among these women, overall chlamydia testing was more frequent among women initiating an IUD (77.8%) than implant initiators (67.8%), p < .001. A similar pattern was seen for gonorrhea testing (80.0% for IUD users, 71.1% for implant users), p < .001. Among sexually active women without chlamydia and gonorrhea testing within the 12 months before the date of insertion, IUD users were more frequently tested for chlamydia (1,410 [20.9%] vs. 433 [9.2%]; p < .001) and for gonorrhea (1,206 [20.0%] vs. 374 [8.9%]; p < .001) than implant users on the day of LARC insertion. CONCLUSIONS: Our results showed that approximately one in four sexually active women undergoing LARC insertion had not received recommended chlamydia and gonorrhea screening past year. Health care providers may use LARC-related visits as an opportunity to educate patients about, and to offer, chlamydia and gonorrhea screening if they had not been screened in the past 12 months.

    • Substance Use and Abuse
      1. Serious mental illness among young people who inject drugs: An assessment of injection risks and healthcare useexternal icon
        Adams M, Sionean C, Broz D, Lewis R, Wejnert C.
        J Infect Dis. 2020 Sep 2;222(Supplement_5):S401-s409.
        BACKGROUND: Data on behavioral correlates of mental illness among young people who inject drugs (PWID) are limited. We examine injection risks and healthcare use among young PWID with probable serious mental illness (PSMI). METHODS: People who inject drugs were recruited and interviewed in 20 US cities for 2015 National HIV Behavioral Surveillance. Probable serious mental illness was assessed using the Kessler-6 screening scale. Bivariate analyses using log-linked Poisson regression with generalized estimating equations adjusted for design covariates were conducted to examine associations between PSMI and behaviors among PWID ages 18-29 years. RESULTS: Of 1769 young PWID, 45% had PSMI. Compared to those without PSMI, PWID with PSMI were more likely to report injecting more than once a day, receptive syringe sharing, sharing of other injection equipment, and unmet needs for medical care and substance use disorder (SUD) treatment. Those with PSMI were less likely to use syringe services programs than those without PSMI. CONCLUSIONS: Approximately half of young PWID had PSMI. People who inject drugs with PSMI engaged in high-risk injection behaviors and encountered barriers to healthcare. Human immunodeficiency virus prevention programs such as Syringe Services Programs (SSPs) could benefit from screening for mental illness among young PWID and strong linkage to healthcare, including mental health and SUD treatment.

      2. Association of e-cigarette advertising with e-cigarette and cigarette use among US adultsexternal icon
        Ali FR, Dave DM, Colman GJ, Wang X, Saffer H, Marynak KL, Dench D, Grossman M.
        Addiction. 2020 Dec 3.
        AIMS: To estimate the association of e-cigarette advertisement exposure with e-cigarette and cigarette use behavior among US adults. DESIGN: Data from the 2013-14 National Adult Tobacco Survey (NATS) were linked to Kantar Media and National Consumer Study data to construct measures of e-cigarette advertisements on TV and in magazines. The relationship between advertisement measures and outcomes was estimated using logistic and Poisson regressions, controlling for socio-demographics, state cigarette taxes and state and year fixed-effects. SETTING: United States. PARTICIPANTS/CASES: A total of 98 746 adults aged ≥ 18 years who responded to the 2013-14 NATS. MEASUREMENTS: The independent variables of interest were the number of e-cigarette advertisements in magazines to which an adult was exposed in the past 6 months and the number of e-cigarette advertisements on TV to which an adult was exposed in the past 6 months. Outcomes were awareness of e-cigarettes, ever e-cigarette use, current e-cigarette use, current cigarette use and number of cigarettes smoked per month. FINDINGS: Exposure to one additional e-cigarette advertisement on TV was associated with a 0.18, 0.13 and 0.03 percentage point increase, respectively, in awareness, ever use and current use of e-cigarettes among all adults (P < 0.05). This exposure also was associated with a 0.11 percentage point increase in current cigarette use among all adults and an increase in cigarette consumption of 2.24 cigarettes per month among adults aged ≥ 45 (P < 0.05). CONCLUSIONS: Exposure to e-cigarette advertising appears to be positively associated with the use of e-cigarettes and cigarettes among adults of all ages, and with increased cigarette consumption among older adults.

      3. Examining the temporality of vitamin E acetate in illicit THC-containing e-cigarette, or vaping, products from a public health and law enforcement response to EVALI - Utah, 2018-2020external icon
        Arons MM, Barnes SR, Cheng R, Whittle K, Elsholz C, Bui D, Gilley S, Maldonado A, LaCross N, Sage K, Lewis N, McCaffrey K, Green J, Duncan J, Dunn AC.
        Int J Drug Policy. 2020 Nov 24;88:103026.
        BACKGROUND: In the summer of 2019, e-cigarette, or vaping, product use-associated lung injury (EVALI) was detected in the United States. Multiple agencies reported illicit tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, products containing vitamin E acetate (VEA) as a substance of concern. METHODS: As an expansion of the Utah Department of Health's response to EVALI, the Utah Public Health Laboratory and the Utah Department of Public Safety screened 170 products from 96 seizures between October 2018 and January 2020. Using Pearson's correlation coefficient, we analyzed the temporal correlation of national, and Utah specific case counts, and the percentage of seizures indicating VEA by month. RESULTS: The findings indicate strong and significant correlations between seizures indicating VEA and both the national (r = 0.70, p = 0.002) and Utah specific (r = 0.78, p < 0.001) case counts. CONCLUSION: These findings underscore that VEA should not be added to e-cigarettes, or vaping, products and the importance of collaboration with law enforcement when responding to outbreaks associated with illicit substances.

      4. Effects of e-cigarette use on cigarette smoking among U.S. youth, 2004-2018external icon
        Creamer MR, Dutra LM, Sharapova SR, Gentzke AS, Delucchi KL, Smith RA, Glantz SA.
        Prev Med. 2020 Nov 19:106316.
        OBJECTIVE: To determine if the declining trend in U.S. youth cigarette smoking changed after e-cigarettes were introduced, and if youth e-cigarette users would have been likely to smoke cigarettes based on psychosocial and demographic predictors of smoking. METHODS: An interrupted time series analysis was used for cross-sectional data from the 2004 to 2018 National Youth Tobacco Surveys (NYTS) to assess changes in cigarette and e-cigarette use over time. A multivariable logistic regression model used 2004-2009 NYTS data on psychosocial risk factors to predict individual-level cigarette smoking risk from 2011 to 2018. Model-predicted and actual cigarette smoking behavior were compared. RESULTS: The decline in current cigarette smoking slowed in 2014 (-0.75 [95% CI: -0.81, -0.68] to -0.26 [95% CI: -0.40, -0.12] percentage points per year). The decline in ever cigarette smoking accelerated after 2012 (-1.45 [95% CI: -1.59, -1.31] to -1.71 [95% CI: -1.75, -1.66]). Ever and current combined cigarette and/or e-cigarette use declined during 2011-2013 and increased during 2013-2014 with no significant change during 2014-2018 for either variable. The psychosocial model estimated that 69.0% of current cigarette smokers and 9.3% of current e-cigarette users (who did not smoke cigarettes) would smoke cigarettes in 2018. CONCLUSIONS: The introduction of e-cigarettes was followed by a slowing decline in current cigarette smoking, a stall in combined cigarette and e-cigarette use, and an accelerated decline in ever cigarette smoking. Traditional psychosocial risk factors for cigarette smoking suggest that e-cigarette users do not fit the traditional risk profile of cigarette smokers.

      5. Toxic metals in liquid and aerosol from pod-type electronic cigarettesexternal icon
        Gray N, Halstead M, Valentin-Blasini L, Watson C, Pappas RS.
        J Anal Toxicol. 2020 Dec 3.
        High quality, accurate data on liquid contents and aerosol emissions from electronic nicotine delivery systems (ENDS, e.g. e-cigarettes) are crucial to address potential health concerns as these devices evolve and mature. Metals are an important class of ENDS constituents that merit attention as they have various health implications. Proper sampling, handling, and aerosol trapping materials are essential to generate accurate quantitative metals data and to reduce the likelihood of inaccurate results originating from inappropriate collection vessels and materials that contribute to high background levels. Published methods that meet these criteria were applied to the analyses of chromium, nickel, copper, zinc, cadmium, tin, and lead in liquid and aerosol from mint/menthol and tobacco flavors of currently popular pod-based devices from 3 manufacturers. Metal concentrations from pods that had not been used for generating aerosol ranged from below our lowest reportable level to 0.164 µg/g for Cr, 61.3 µg/g for Ni, 927 µg/g for Cu, 14.9 µg/g for Zn, 58.2 µg/g for Sn, and 2.56 µg/g for Pb. Cadmium was included in our analyte panel and was not present above detection limits in liquid or aerosol. Aerosol metal concentrations (using a 55 mL puff) ranged from below our lowest reportable level to 29.9 ng/10 puffs for Cr, 373 ng/10 puffs for Ni, 209 ng/10 puffs for Cu, 4,580 ng/10 puffs for Zn, 127 ng/10 puffs for Sn, and 463 ng/10 puffs for Pb. Our results showed some metals delivery from all the products examined and highly variable metal levels between manufacturer, brand, and package.

      6. BACKGROUND: The opioid overdose epidemic has been declared a public health emergency. Women are more likely than men to be prescribed opioid medications. Some states have adopted policies to improve opioid prescribing, including prescription drug monitoring programs (PDMPs) and pain clinic laws. OBJECTIVE: Among reproductive-aged women, we examined the association of mandatory use laws for PDMPs in Kentucky (concurrent with a pain clinic law) and New York with overdose involving prescription opioids or heroin and opioid use disorder (OUD). STUDY DESIGN, SUBJECTS, AND OUTCOME MEASURES: We conducted interrupted time series analyses estimating outcome changes after policy implementation in Kentucky and New York, compared with geographically close states without these policies (comparison states), using 2010-2014 State Inpatient and State Emergency Department Databases. Outcomes included rates of inpatient discharges and emergency department visits for overdoses involving prescription opioids or heroin and OUD among reproductive-aged women. RESULTS: Relative to comparison states, following Kentucky's policy change, we found an immediate postpolicy decrease and a decreasing trend in the rate of overdoses involving prescription opioids, an immediate postpolicy increase in the rate of overdoses involving heroin, and a decreasing trend in the OUD rate (P<0.01); New York's policy change was not associated with the assessed outcomes. CONCLUSIONS: PDMPs and pain clinic laws, such as those implemented in Kentucky, may be promising strategies to reduce the adverse impacts of high-risk opioid prescribing among reproductive-aged women. As states continue efforts to improve inappropriate opioid prescribing, similar strategies as those adopted in Kentucky merit consideration.

      7. Youth e-cigarette use has rapidly increased in the last few years. Susceptibility is a validated measure associated with future tobacco use. We examined trends in e-cigarette susceptibility across five years (2014-2018) of the National Youth Tobacco Survey among youth e-cigarette never users. We observed increases in overall e-cigarette susceptibility from 2014 to 2016 and decreases from 2016 to 2018. Generally, sociodemographic variables were not associated with trend effects; however, there was an interaction between linear trends with both race/ethnicity and other tobacco product (OTP) use. The percentage of youth who were susceptible to using e-cigarettes ranged from 32.9% in 2014 to 33.2% in 2018 with a high of 36.7% in 2016. We also examined the prevalence of e-cigarette susceptibility by race/ethnicity, sex, school level, OTP use, and e-cigarette harm perception. E-cigarette susceptibility was associated with race, school level, OTP ever use, and e-cigarette harm perceptions. Hispanic youth, those in high school, and OTP ever users were more likely to be susceptible to e-cigarette use compared to their counterparts across all years. E-cigarette susceptibility was most prevalent among those who perceived e-cigarettes to pose "no harm" in 2014 and "little harm" in 2018 when compared to other item response options in 2014 and 2018, respectively. This study is the first to document trends in e-cigarette susceptibility among youth. Understanding antecedents of e-cigarette use and identifying youth subgroups vulnerable to e-cigarette use is valuable to developing effective prevention efforts. Disclaimer: The findings and conclusions in this publication are those of the authors and do not necessarily represent the official position of the Food and Drug Administration or the Centers for Disease Control and Prevention.

      8. Suspected nonfatal drug-related overdoses among youth in the US: 2016-2019external icon
        Roehler DR, Olsen EO, Mustaquim D, Vivolo-Kantor AM.
        Pediatrics. 2020 Dec 7.
        BACKGROUND AND OBJECTIVES: During the current drug overdose crisis, the United States is experiencing a significant number of overdose deaths, hospitalizations, and emergency department visits. Given the vulnerability of young persons to substance use, it is important to assess how this crisis affects the nation's youth. In this study, we investigate trends in suspected nonfatal drug-related overdoses (all-drugs, opioids, heroin, and stimulants) among youth using syndromic surveillance data from 2016 to 2019. METHODS: A retrospective analysis of emergency department syndromic surveillance data were used to detect quarterly trends in suspected drug overdoses from April 2016 through September 2019 among youth aged 0 to 10, 11 to 14, and 15 to 24 years. Syndrome definitions were developed using chief complaint free-text and discharge diagnosis codes to identify overdoses involving all-drugs, opioids, heroin, and stimulants. Pearson χ(2) tests detected quarter-to-quarter changes, and joinpoint regression analysis assessed trends over time. RESULTS: On average, there was a 2.0 increase for youth aged 0 to 10 years and a 2.3 increase for youth aged 11 to 14 years for suspected all-drug overdoses. Suspected heroin overdoses decreased by an average of 3.3 per quarter for youth aged 15 to 24 years. Among all age groups, suspected stimulant overdoses increased across the study period, 3.3 for 0 to 10-year-olds, 4.0 for 11- to 14-year-olds, and 2.3 for 15- to 24-year-olds. CONCLUSIONS: Suspected stimulant-involved drug overdoses appear to be rising among youth. These findings could inform targeted interventions, such as stimulant-focused prevention, and comprehensive approaches, including school-based prevention and other strategies to lower morbidity and mortality.

      9. Characteristics and correlates of recent successful cessation among adult cigarette smokers, United States, 2018external icon
        Walton K, Wang TW, Prutzman Y, Jamal A, Babb SD.
        Prev Chronic Dis. 2020 Dec 10;17:E154.
        We assessed characteristics and correlates of recent successful cessation (quitting smoking for 6 months or longer within the past year) among US adult cigarette smokers aged 18 years or older. Estimates came from the July 2018 fielding of the 2018-2019 Tobacco Use Supplement to the Current Population Survey (N = 26,759). In 2018, 7.1% of adult smokers reported recent successful cessation. Recent successful cessation varied by certain demographic characteristics, noncigarette tobacco product use, smoke-free home rules, and receipt of advice to quit from a medical doctor. To help more smokers quit, public health practitioners can ensure that evidence-based tobacco control interventions, including barrier-free access to evidence-based cessation treatments, are reaching all tobacco users, especially those who face greater barriers to quitting.

    • Zoonotic and Vectorborne Diseases
      1. Serological evidence of human infections with highly pathogenic avian influenza A(H5N1) virus: a systematic review and meta-analysisexternal icon
        Chen X, Wang W, Wang Y, Lai S, Yang J, Cowling BJ, Horby PW, Uyeki TM, Yu H.
        BMC Med. 2020 Dec 2;18(1):377.
        BACKGROUND: Highly pathogenic avian influenza A(H5N1) virus poses a global public health threat given severe and fatal zoonotic infections since 1997 and ongoing A(H5N1) virus circulation among poultry in several countries. A comprehensive assessment of the seroprevalence of A(H5N1) virus antibodies remains a gap and limits understanding of the true risk of A(H5N1) virus infection. METHODS: We conducted a systematic review and meta-analysis of published serosurveys to assess the risk of subclinical and clinically mild A(H5N1) virus infections. We assessed A(H5N1) virus antibody titers and changes in titers among populations with variable exposures to different A(H5N1) viruses. RESULTS: Across studies using the World Health Organization-recommended seropositive definition, the point estimates of the seroprevalence of A(H5N1) virus-specific antibodies were higher in poultry-exposed populations (range 0-0.6%) and persons exposed to both human A(H5N1) cases and infected birds (range 0.4-1.8%) than in close contacts of A(H5N1) cases or the general population (none to very low frequencies). Seroprevalence was higher in persons exposed to A(H5N1) clade 0 virus (1.9%, range 0.7-3.2%) than in participants exposed to other clades of A(H5N1) virus (range 0-0.5%) (p < 0.05). Seroprevalence was higher in poultry-exposed populations (range 0-1.9%) if such studies utilized antigenically similar A(H5N1) virus antigens in assays to A(H5N1) viruses circulating among poultry. CONCLUSIONS: These low seroprevalences suggest that subclinical and clinically mild human A(H5N1) virus infections are uncommon. Standardized serological survey and laboratory methods are needed to fully understand the extent and risk of human A(H5N1) virus infections.

      2. Notes from the field: Interpretation of rapid diagnostic tests for leptospirosis during a dengue outbreak - Yap State, Federated States of Micronesia, 2019external icon
        Dawson P, Marfel M, Galloway R, Tareg A, Paz-Bailey G, Muñoz-Jordán JL, Sharp TM, Adams LE, Bower WA.
        MMWR Morb Mortal Wkly Rep. 2020 Dec 4;69(48):1832-1833.

      3. Dengue fever (DF) is a viral infection that is common in tropical countries and represents a significant cause of global morbidity and mortality. Despite its prevalence and severity, treatment options for DF remain limited and consist primarily of supportive measures. Several recent studies have concluded that micronutrient supplementation may improve clinical outcomes in patients with DF, but no review has summarized and synthesized these findings. We conducted a literature review to identify articles investigating the effect of micronutrient supplementation on clinical outcomes among patients with DF. We found several studies which indicated that supplemental vitamin C, vitamin D, vitamin E, and zinc may be useful adjuncts in DF treatment. Folic acid supplementation did not appear to affect clinical outcomes. The reviewed studies have significant limitations including small sample sizes and limited data about the baseline nutritional status of study subjects. We identify a need for additional high-quality randomized trials to elucidate the role of micronutrient supplementation in DF treatment.

      4. Analyses of the performance of the Ebola virus disease alert management system in South Sudan: August 2018 to November 2019external icon
        Olu OO, Lako R, Bunga S, Berta K, Kol M, Ramadan PO, Ryan C, Udenweze I, Guyo AG, Conteh I, Huda Q, Gai M, Saulo D, Papowitz H, Gray HJ, Chimbaru A, Wangdi K, Grube SM, Barr BT, Wamala JF.
        PLoS Negl Trop Dis. 2020 Nov 30;14(11):e0008872.
        South Sudan implemented Ebola virus disease preparedness interventions aiming at preventing and rapidly containing any importation of the virus from the Democratic Republic of Congo starting from August 2018. One of these interventions was a surveillance system which included an Ebola alert management system. This study analyzed the performance of this system. A descriptive cross-sectional study of the Ebola virus disease alerts which were reported in South Sudan from August 2018 to November 2019 was conducted using both quantitative and qualitative methods. As of 30 November 2019, a total of 107 alerts had been detected in the country out of which 51 (47.7%) met the case definition and were investigated with blood samples collected for laboratory confirmation. Most (81%) of the investigated alerts were South Sudanese nationals. The alerts were identified by health workers (53.1%) at health facilities, at the community (20.4%) and by screeners at the points of entry (12.2%). Most of the investigated alerts were detected from the high-risk states of Gbudwe (46.9%), Jubek (16.3%) and Torit (10.2%). The investigated alerts commonly presented with fever, bleeding, headache and vomiting. The median timeliness for deployment of Rapid Response Team was less than one day and significantly different between the 6-month time periods (K-W = 7.7567; df = 2; p = 0.0024) from 2018 to 2019. Strengths of the alert management system included existence of a dedicated national alert hotline, case definition for alerts and rapid response teams while the weaknesses were occasional inability to access the alert toll-free hotline and lack of transport for deployment of the rapid response teams which often constrain quick response. This study demonstrates that the Ebola virus disease alert management system in South Sudan was fully functional despite the associated challenges and provides evidence to further improve Ebola preparedness in the country.

      5. Parental stress in primary caregivers of children with evidence of congenital Zika virus infection in northeastern Brazilexternal icon
        Ornelas Pereira I, Santelli AC, Leite PL, Attell J, Bertolli J, Kotzky K, Araújo WN, Peacock G.
        Matern Child Health J. 2020 Nov 27.
        BACKGROUND: Despite the well-known role of parents as caregivers, few studies have addressed their health outcomes related to the Zika virus epidemic. METHODS: A cross-sectional study was carried out with 146 primary caregivers of children 15-26 months of age, with laboratory and/or clinical evidence of Zika infection between August and October 2017 in three Brazilian municipalities: João Pessoa and Campina Grande in the state of Paraíba and Fortaleza in the state of Ceará. Caregivers reported on their child's life and health, family circumstances and underwent screening for stress using the Parenting Stress Index-Short Form. Children were evaluated for developmental delays and clinical outcomes. Differences in the prevalence of risk factors between caregivers with high or clinically relevant stress and those with normal stress were evaluated. RESULTS: Of the 146 participants, 13% (n = 19) were classified as having high or clinically relevant stress, all of them mothers. The two risk factors significantly and independently associated with high levels of stress, compared with individuals with normal stress levels, were "reporting difficulty in covering basic expenses" (adjusted OR 3.6 (95% CI 1.1-11.8; p = 0.034)) and "having a child with sleep problems" (adjusted OR 10.4 (95% CI 1.3-81.7; p = 0.026)). CONCLUSIONS: Some factors seem to contribute significantly more than others to the level of stress experienced by caregivers of children with evidence of Zika virus congenital infection. Interventions and preventive strategies should also target caregivers, who in turn will be able to respond to the unique characteristics of their child.

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DISCLAIMER: Articles listed in the CDC Science Clips are selected by the Stephen B. Thacker CDC Library to provide current awareness of the public health literature. An article's inclusion does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.

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